Trial Outcomes & Findings for A Phase II Trial If Nivolumab, Lenalidomide and Dexamethasone in High Risk Smoldering Myeloma (NCT NCT02903381)

NCT ID: NCT02903381

Last Updated: 2023-06-13

Results Overview

The primary endpoint will be the 2-year progression-free percent and will be reported with corresponding 90% confidence interval. All patients who have received one dose of study treatment will be included for the analysis, including those who die or are lost to follow-up before 2 years. Progression is defined as ≥ 25% increase and an absolute increase of ≥ 0.5g/dL from their nadir in their serum or urine m-spike or FLC with no CRAB features attributable to MM progression.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: 2 Year
• Results posted on: 2023-06-13

Participant Flow

Participant milestones

Measure	Nivolumab, Lenalidomide, Dexamethasone * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase II Trial If Nivolumab, Lenalidomide and Dexamethasone in High Risk Smoldering Myeloma

Baseline characteristics by cohort

Measure	Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 Participants n=5 Participants
ECOG Performance Status 00 - Fully Active	5 Participants n=5 Participants
ECOG Performance Status 01 - Restricted	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 Year

Population: All patients receiving any amount of protocol treatment. Patients who have progressed or lost to follow-up prior to two years are counted as failures; only patients followed and progression-free for at least two years are counted as successes.

The primary endpoint will be the 2-year progression-free percent and will be reported with corresponding 90% confidence interval. All patients who have received one dose of study treatment will be included for the analysis, including those who die or are lost to follow-up before 2 years. Progression is defined as ≥ 25% increase and an absolute increase of ≥ 0.5g/dL from their nadir in their serum or urine m-spike or FLC with no CRAB features attributable to MM progression.

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

2 Year Progression Free Percent

62.5 percentage of participants Interval 28.9 to 88.9

SECONDARY outcome

Timeframe: 2 Years

The percent of patients with objective response defined as achieving a partial response or better according to the modified International Myeloma Working Group (IMWG) criteria

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Objective Response Percent

87.5 percentage of participants Interval 52.9 to 99.4

SECONDARY outcome

Timeframe: Baseline to documented progression, up to 24 months post initiation of therapy.

Time to progression (TTP) is defined as the time from protocol therapy initiation until documented progression, censored at date last known progression-free for those who have not progressed, up to 24 months post initiation of therapy.

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Time to Progression Probability at 2-years

0.75 probability Interval 0.54 to 1.0

SECONDARY outcome

Timeframe: time from objective response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died, up to 24 months post initiation of therapy.

Population: 7 of 8 patients achieved a confirmed objective response and are included in duration of response analysis

Kaplan-Meier method, duration of response probability in patients with partial response or better. Events defined as confirmed progression or death from any cause

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=7 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Duration of Response Probability at 2-years

0.71 probability Interval 0.48 to 1.0

SECONDARY outcome

Timeframe: Baseline to disease progression or death from any cause, censored at date last known progression free for those who have not progressed or died, up to 24 months post initiation of therapy.

Kaplan-Meier method, percent of patients alive and progression-free at 2-years

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Progression Free Survival (PFS) Probability at 2-years

0.75 probability Interval 0.54 to 1.0

SECONDARY outcome

Timeframe: Baseline to death or date last known alive, up to 24 months post initiation of therapy.

Kaplan-Meier method, percent alive at 2-years

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Overall Survival Probability at 2-years

1.0 probability Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: 2 Years

It is expected that approximately 20% of the patients will receive cyclophosphamide (CTX) for mobilization and this may influence the PFS. Therefore, in a secondary analysis the 2 year PFS rate will be evaluated among those patients who did not receive CTX.

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=7 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Progression Free Survival Rate-Without Cyclophosphamide

71.4 percentage of participants Interval 48.2 to 100.0

SECONDARY outcome

Timeframe: Baseline to 2 Years

For toxicity reporting, all adverse events and laboratory abnormalities will be graded and analyzed using CTCAE version 4 as appropriate.

Outcome measures

Measure

Nivolumab, Lenalidomide, Dexamethasone n=8 Participants * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6

Number of Participants With Adverse Events

8 Participants

Adverse Events

Nivolumab, Lenalidomide, Dexamethasone

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nivolumab, Lenalidomide, Dexamethasone n=8 participants at risk * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6
Investigations Alanine aminotransferase increased	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Aspartate aminotransferase increased	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Infections and infestations Lung infection	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.

Other adverse events

Measure	Nivolumab, Lenalidomide, Dexamethasone n=8 participants at risk * A treatment cycle is defined as 28 consecutive days. * Participants will receive 6 cycles of induction therapy followed by 6 cycles of maintenance therapy with lower doses of lenalidomide and no dexamethasone for a total of 12 months. Nivolumab: Intravenous, predetermined dosage, Days 1 and 15 during cycles 1-12 and Lenalidomide: Oral, predetermined dosage, Days 1-21 of cycle 1-12 Dexamethasone: Oral, Days 1, 8, 15 of cycle 1-6
General disorders Fatigue	75.0% 6/8 • Number of events 9 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Neutrophil count decreased	75.0% 6/8 • Number of events 21 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Blood and lymphatic system disorders Anemia	62.5% 5/8 • Number of events 14 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hypophosphatemia	62.5% 5/8 • Number of events 10 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Skin and subcutaneous tissue disorders Rash maculo-papular	62.5% 5/8 • Number of events 7 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations White blood cell decreased	62.5% 5/8 • Number of events 14 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Gastrointestinal disorders Constipation	50.0% 4/8 • Number of events 7 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
General disorders Edema limbs	50.0% 4/8 • Number of events 5 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hypoalbuminemia	50.0% 4/8 • Number of events 7 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Musculoskeletal and connective tissue disorders Myalgia	50.0% 4/8 • Number of events 5 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Platelet count decreased	50.0% 4/8 • Number of events 11 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Musculoskeletal and connective tissue disorders Arthralgia	37.5% 3/8 • Number of events 3 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Gastrointestinal disorders Diarrhea	37.5% 3/8 • Number of events 3 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Dizziness	37.5% 3/8 • Number of events 3 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Respiratory, thoracic and mediastinal disorders Dyspnea	37.5% 3/8 • Number of events 3 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Endocrine disorders Hyperthyroidism	37.5% 3/8 • Number of events 5 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Psychiatric disorders Insomnia	37.5% 3/8 • Number of events 3 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Alanine aminotransferase increased	25.0% 2/8 • Number of events 4 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Aspartate aminotransferase increased	25.0% 2/8 • Number of events 4 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Eye disorders Blurred vision	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Creatinine increased	25.0% 2/8 • Number of events 4 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Dysgeusia	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Vascular disorders Flushing	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hyperglycemia	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hyperkalemia	25.0% 2/8 • Number of events 5 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hypocalcemia	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Endocrine disorders Hypothyroidism	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Vascular disorders Thromboembolic event	25.0% 2/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Investigations Blood bilirubin increased	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Gastrointestinal disorders Dry mouth	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
General disorders Edema face	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Eye disorders Eye disorders - Other, specify	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Headache	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Respiratory, thoracic and mediastinal disorders Hiccups	12.5% 1/8 • Number of events 2 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Respiratory, thoracic and mediastinal disorders Hoarseness	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hypokalemia	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hypomagnesemia	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Metabolism and nutrition disorders Hyponatremia	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Infections and infestations Laryngitis	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Psychiatric disorders Libido decreased	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
General disorders Localized edema	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Infections and infestations Mucosal infection	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Musculoskeletal and connective tissue disorders Neck pain	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Nervous system disorders - Other, specify	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
General disorders Pain	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Skin and subcutaneous tissue disorders Periorbital edema	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Peripheral motor neuropathy	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Nervous system disorders Peripheral sensory neuropathy	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Skin and subcutaneous tissue disorders Pruritus	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Skin and subcutaneous tissue disorders Scalp pain	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Infections and infestations Sinusitis	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Respiratory, thoracic and mediastinal disorders Sore throat	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Vascular disorders Superficial thrombophlebitis	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.
Infections and infestations Urinary tract infection	12.5% 1/8 • Number of events 1 • Adverse Events or toxicity events assessed/monitored from the day of consent up to end of treatment visit for an average of 14 months. All-Cause Mortality as well as Serious Adverse Events were assessed up to 4.5 years. Toxicity assessments performed on day 1 of cycles 1-12 (each cycle is 28 days); additional assessment on end-of-treatment visit. Reported toxicities have either "definite," "probable," or "possible" attribution to any of protocol treatments.

Additional Information

Dr. Irene Ghobrial

Dana-Farber Cancer Institute

Phone: 617-632-4198

Email: irene_ghobrial@dfci.harvard.edu

Results disclosure agreements

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