Trial Outcomes & Findings for Lenalidomide in Older Patients With Acute Myeloid Leukemia Without Chromosome 5q Abnormalities (NCT NCT00546897)

NCT ID: NCT00546897

Last Updated: 2014-09-29

Results Overview

CRm = Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1000/uL, platelet count \>100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. CRi = Defined as CR with the exception of neutropenia \<1000/uL or thrombocytopenia \<100,000/ul. Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 48 participants
• Primary outcome timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)
• Results posted on: 2014-09-29

Participant Flow

The study opened to participant enrollment on 02/02/2007 and closed to participant enrollment on 03/04/2009.

Participant milestones

Measure	Cohort 1 Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Overall Study STARTED	15	33
Overall Study COMPLETED	15	33
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lenalidomide in Older Patients With Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

Baseline characteristics by cohort

Measure	Cohort 1 n=15 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.	Total n=48 Participants Total of all reporting groups
Age, Continuous	71 years n=5 Participants	71 years n=7 Participants	71 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	33 participants n=7 Participants	48 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	10 participants n=5 Participants	16 participants n=7 Participants	26 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	4 participants n=5 Participants	13 participants n=7 Participants	17 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Cytogenetic Risk Category Intermediate	13 participants n=5 Participants	18 participants n=7 Participants	31 participants n=5 Participants
Cytogenetic Risk Category Unfavorable	2 participants n=5 Participants	13 participants n=7 Participants	15 participants n=5 Participants
Cytogenetic Risk Category Unknown	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.

CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.

Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Complete Remission Rate (CRm + CRi + CRc) CRm	0 participants	3 participants
Complete Remission Rate (CRm + CRi + CRc) CRi	0 participants	4 participants
Complete Remission Rate (CRm + CRi + CRc) CRc	1 participants	3 participants

SECONDARY outcome

Timeframe: 4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)]

Toxicity will be scored using CTCAE Version 3.0 for toxicity and adverse event reporting

Outcome measures

Measure	Cohort 1 n=15 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Safety and Tolerability (Removal From Study Due to Adverse Events)	1 participants	8 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

RR = as patients obtaining any response (CRm + CRc +CRi + PR).

CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.

CRc = Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.

Partial remission (PR): Requires

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Response Rate (RR) CRc	1 participants	3 participants
Response Rate (RR) CRm	0 participants	3 participants
Response Rate (RR) CRi	0 participants	4 participants
Response Rate (RR) PR	1 participants	0 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

Morphologic leukemia-free state: Defined as < 5% blasts on the BM aspirate with spicules and a count of > 200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease.

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Morphologic Leukemia Free State	1 participants	10 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Morphologic Complete Remission Rate (CRm)	0 participants	3 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Cytogenetics CR Rate (CRc)	1 participants	3 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
CR With Complete Blood Counts (CRi) Rate	0 participants	4 participants

SECONDARY outcome

Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Population: 9 out of 15 participants did not receive the two low dose cycles of lenalidomide in Cohort 1. 23 out of 33 participants did not receive the two low dose cycles of lenalidomide in Cohort 2.

Partial remission (PR): Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission.

Outcome measures

Measure	Cohort 1 n=6 Participants Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Partial Remission Rate (PR)	1 participants	0 participants

SECONDARY outcome

Timeframe: 2 years

Population: Participants in Cohort 1 were not analyzed for overall survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease.

Overall survival: Defined as the date of first dose of study drug to the date of death from any cause.

Outcome measures

Measure	Cohort 1 Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Overall Survival (OS)	—	4 months Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: 2 years

Population: Event free survival was not analyzed. Progression free survival was analyzed instead.

Event free survival: Defined as the interval from the date of first dose of study drug to date of treatment failure, recurrence, or death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

Population: Participants in Cohort 1 were not analyzed for progression-free survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease.

Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment. It is the percentage of individuals in the group whose disease is likely to remain stable (and not show signs of progression) after a specified duration of time. Progression-free survival rates are an indication of how effective a particular treatment is.

Outcome measures

Measure	Cohort 1 Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Progression-free Survival	—	2 months Interval 2.0 to 3.0

SECONDARY outcome

Timeframe: 2 years

Population: Participants in Cohort 1 were not analyzed for relapse free survival because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease.

This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause.

Outcome measures

Measure	Cohort 1 Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Relapse Free Survival (RFS) for Complete Responders	—	10 months Interval 2.0 to NA = this is NE (not estimated). The upper bound of the 95% confidence interval was not estimable using the Kaplan-Meier survival curve

SECONDARY outcome

Timeframe: 2 years

Population: Participants in Cohort 1 were not analyzed for duration of remission because it was determined the treatment design did not work. 8 out of 15 participants did not receive the 2 high dose lenalidomide cycles and 9 out of 15 participants did not receive any of the low dose lenalidomide cycles due to progressive disease.

Duration of remission: Defined as the interval from the date complete remission is documented to the date of recurrence

Outcome measures

Measure	Cohort 1 Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=10 Participants Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Duration of CR for Complete Responders	—	10 months Interval 1.0 to 17.0

SECONDARY outcome

Timeframe: Baseline, during therapy, and posttherapy

Population: This outcome was not analyzed for either Cohort due to number of samples collected.

Peripheral blood mononuclear cells (PBMC) will be viably cryopreserved from patients at baseline (pre-therapy, newly diagnosed AML), during lenalidomide therapy, and posttherapy. Following sample collection, PBMC will be thawed, and flow cytometry will be performed to assess NK cell number (CD56+CD3-), subsets, and phenotype utilizing the Siteman Cancer Center Flow Cytometry / Cell Sorting Core. In addition, NK cell function will be assessed in flow based killing assays using PBMC (containing NK cells) as effectors and NK sensitive cell lines (K562) and/or autologous leukemic blasts as target cells. Thus, analyzing these parameters in patients before, during, and after therapy will provide a comprehensive evaluation of the ability of lenalidomide to modulate NK cells in patients in vivo.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre and post treatment

Population: This outcome measure was not analyzed for either Cohort due to sample collection.

RNA will be made from total bone marrow cells for labeling and evaluations by RNA profiling. Cellular RNA and corresponding biotinylated cRNA targets will be prepared and hybridized with Affymetrix GeneChip® microarrays within the Multiplexed Gene Analysis SCC Core (Dr. Mark Watson, Director). Microarray data (and eventually corresponding gene sequence data) will be integrated an analyzed with state-of-the-art software packages. The pre- and post-treatment RNA profiling studies will be used as a discovery tool. Patterns of gene expression before and after lenalidomide therapy will be compared within each patient's sample to identify genes with altered expression after lenalidomide therapy. In addition, supervised algorithms will be sued to identify genes that can potentially predict clinical outcome and response to lenalidomide therapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre and post treatment

Population: This outcome was not analyzed for either Cohort due to sample collection.

Proteomic analysis will be performed within the Siteman Cancer Center proteomics core on pre- and post-treatment plasma samples. This pilot proteomic study will identify candidate proteins of interest with altered expression after treatment with lenalidomide. This approach will provide an unbiased method to assess global changes in serum proteins following lenalidomide therapy.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1

Serious events: 10 serious events

Other events: 15 other events

Deaths: 0 deaths

Cohort 2

Serious events: 25 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1 n=15 participants at risk Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 participants at risk Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Blood and lymphatic system disorders Febrile neutropenia	40.0% 6/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Pneumonia	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	27.3% 9/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Gouty arthritis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Nausea	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Vomiting	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Headache	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Death due to progressive disease	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Staph hominis bacteremia infection	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Catheter line infection	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Diarrhea	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dehydration	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Opportunistic fungal infection - death	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Lower extremity weakness	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Fatigue	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dysphagia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Rash	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Syncope	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Petichae	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Metabolism and nutrition disorders Failure to thrive	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Death due to CNS hemorrhage	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Gram-cocci infection	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Metabolism and nutrition disorders Anorexia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypernatremia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypokalemia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Neutrophils	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Platelets	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Splenic infarction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Streptococcus bacteremia infection	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Death due to acute renal failure	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Myocardial infarction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Chest pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Subdural hematoma	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations E. Coli infection	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Blood and lymphatic system disorders Hemoglobin	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Constipation	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Mucositis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Oral candidiasis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Sinusitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Coryn bacterium miutissimum sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Staphylcoccus epidermidis sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Renal failure	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Mental status	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Gram positive sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Hepatobiliary disorders Liver dysfunction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Tonsil fistula	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Coagulase negative staphylococcus sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Cardiac ischemia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders C. difficile colitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Upper GI hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Lower GI hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Left ventricular diastolic dysfunction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Urinary tract infection	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).

Other adverse events

Measure	Cohort 1 n=15 participants at risk Lenalidomide 50 mg/day oral for 14 days followed by 30 days of rest. Lenalidomide 50 mg/day oral for 21 days (this is Cycle 1 and Cycle 2). If no progressive disease (PD) then lenalidomide 10 mg/day oral for 28 days for 12 cycles.	Cohort 2 n=33 participants at risk Cycle 1: Oral lenalidomide 50 mg/day x 28 days induction therapy. Treatment will then depend on the response to Cycle 1: if patients obtain a complete remission (CR) they will proceed to low dose lenalidomide therapy, if patients have a non-CR they will receive a second high dose cycle of lenalidomide 50 mg/day x 28 days (Cycle 2) Cycle 2 consists of lenalidomide 50mg/day x 28 days Further treatment will depend on the response to Cycle 2: if patients obtain a CR/partial remission (PR)/stable disease (SD) they will proceed to low dose lenalidomide therapy, if patients have PD they will be removed from the study. Low Dose Cycles: low dose lenalidomide therapy consisting of 10 mg daily for a 28 day cycle.be 1) For patients that achieve a CR, 2 cycles of low dose lenalidomide will be administered, and then patients observed off therapy. For patients with PR/SD, low dose lenalidomide will continue for a total of 6 cycles and then patients will be observed off therapy.
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	21.2% 7/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Acne	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Alkaline phosphatase	26.7% 4/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	30.3% 10/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Alkylosis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Immune system disorders Allergic reaction/hypersensitivity	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Metabolism and nutrition disorders Anorexia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Arthritis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Atrial fibrillation	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Back pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Back spasms	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Bilirubin	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Surgical and medical procedures Biopsy site pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Eye disorders Blurred vision	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Bone pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders CNS hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Cardiac ischemia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Cardiopulmonary arrest	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Chest pain	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Chest wall pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Chills	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Confusion	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Constipation	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Cough	33.3% 5/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	30.3% 10/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Creatinine	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Cystitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Decubitus	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dehydration	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dental abscess	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dental pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Diarrhea	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Diverticulosis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Dizziness	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dry mouth	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Dysphagia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Dyspnea	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	39.4% 13/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Edema	46.7% 7/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Erythema	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Esophagitis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Eye disorders Eye hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Fatigue	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	51.5% 17/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Blood and lymphatic system disorders Febrile neutropenia	33.3% 5/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	42.4% 14/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Feet pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Fever (no infection)	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Flank pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Flatulence	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Eye disorders Floaters	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Generalized pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	21.2% 7/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Hand pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Hard palate ulcer	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Headache	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Vascular disorders Hematoma	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Blood and lymphatic system disorders Hemoglobin	66.7% 10/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	66.7% 22/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Vascular disorders Hemorrhagic lesion	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Hemorrhoid pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Hiccups	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hyperglycemia	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hyperkalemia	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypermagnesemia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypernatremia	33.3% 5/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Hypertension	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hyperuricemia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypoalbuminemia	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	57.6% 19/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypocalcemia	80.0% 12/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	63.6% 21/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypokalemia	26.7% 4/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	42.4% 14/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hyponatremia	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Hypophosphatemia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Hypotension	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Endocrine disorders Hypothyroidism	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations INR	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Incontinence - anal	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - cellulitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - clostridium difficile	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - enterococcus faecium	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - escheria coli	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - oral candidiasis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - parainfluenza	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - pneumonia	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - polymicrobial sepsis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - stapphylococcus	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - unspecified	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - upper respiratory	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - urinary tract	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/neutropenia - vaginal	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - bronchitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - catheter fungemia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - coagulase negative staphylococcus bacteremia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - middle ear	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - oral candidiasis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - pneumonia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Infection w/o neutropenia - upper respiratory	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Inguinal hernia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Insomnia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Knee pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Left ventricular systolic dysfunction	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Leukocytes (WBC)	60.0% 9/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	45.5% 15/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Hepatobiliary disorders Liver dysfunction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Lower GI NOS hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Lower back pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Blood and lymphatic system disorders Lymphocele	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Lymphopenia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Mood alteration - agitation	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Mood alteration - anxiety	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Mood alteration - depression	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Mucositis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Muscle pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Muscle weakness - generalized	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Muscle weakness - lower extremity	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Nausea	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	27.3% 9/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Neck nodule	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Neutrophils (ANC)	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	33.3% 11/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Nose bleed	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Palpitations	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Peridontal - mandible swelling	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Periodontal - poor dentition	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Vascular disorders Petechiae	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Platelets	80.0% 12/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	75.8% 25/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Progressive disease	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	15.2% 5/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Pruritis	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Psychiatric disorders Psychosis - hallucinations	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Rash	40.0% 6/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	54.5% 18/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Renal failure	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Rib pain	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations SGOT (AST)	53.3% 8/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	36.4% 12/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations SGPT (ALT)	80.0% 12/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	42.4% 14/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Sensory neuropathy	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Shoulder pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Sinus bradycardia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Sinus drainage	20.0% 3/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Sinus tachycardia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	21.2% 7/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Infections and infestations Sinusitis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Skin and subcutaneous tissue disorders Skin sore	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Spinal stenosis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Splenic infarction	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Supraventricular arrhythmia	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
General disorders Sweating	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Syncope	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Taste alteration	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Respiratory, thoracic and mediastinal disorders Throat pain	13.3% 2/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	9.1% 3/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Vascular disorders Thrombosis	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Tingling in extremities	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	6.1% 2/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Tonsil fistula	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Nervous system disorders Tremors	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Musculoskeletal and connective tissue disorders Upper extremity pain	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Urinary frequency	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Renal and urinary disorders Urinary incontinence	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	12.1% 4/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Vascular disorders Vasculitis	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	0.00% 0/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Cardiac disorders Ventricular tachycardia	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Gastrointestinal disorders Vomiting	6.7% 1/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	18.2% 6/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).
Investigations Weight loss	0.00% 0/15 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).	3.0% 1/33 • Adverse events were collected from the start of treatment until 30 days following the completion of treatment. Cohort 1 median duration of treatment was 65 days (5-530). Cohort 2 median duration of treatment was 65 days (3-413).

Additional Information

Ravi Vij, M.D.

Washington University School of Medicine

Phone: 314-454-8304

Email: rvij@dom.wustl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place