Trial Outcomes & Findings for EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma (NCT NCT01000285)

NCT ID: NCT01000285

Last Updated: 2017-03-28

Results Overview

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: Up to 30 days after completion of treatment
• Results posted on: 2017-03-28

Participant Flow

The study opened to participant enrollment on 12/22/2010 and closed to participant enrollment on 05/29/2014.

Participant milestones

Measure	EPOCH Chemotherapy & Bortezomib Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Overall Study STARTED	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma

Baseline characteristics by cohort

Measure	Acute ATLL n=6 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Lymphoma ATLL n=12 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Total n=18 Participants Total of all reporting groups
Age, Continuous	51.5 years n=93 Participants	56 years n=4 Participants	52 years n=27 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	10 Participants n=4 Participants	14 Participants n=27 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment United States	6 participants n=93 Participants	12 participants n=4 Participants	18 participants n=27 Participants
Birthplace Antigua	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Birthplace Dominican Republic	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Birthplace Haiti	0 participants n=93 Participants	3 participants n=4 Participants	3 participants n=27 Participants
Birthplace Jamaica	3 participants n=93 Participants	5 participants n=4 Participants	8 participants n=27 Participants
Birthplace USA	1 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants
Birthplace Virgin Islands	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Birthplace Bahamas	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 30 days after completion of treatment

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=18 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Fatigue	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Vomiting	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Spontaneous bacterial peritonitis	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Abdominal distension	2 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Hemoglobin	6 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Leukocytes (WBC)	7 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Lymphopenia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Neutrophils	6 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Platelets	6 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Infection without neutropenia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Infection with neutropenia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Omaya port infection	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events IV port infection	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Sepsis	2 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Neutropenic fever	3 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Hypoglycemia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Hyperglycemia	2 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Magnesium	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Hypokalemia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Hypertriglyceridemia	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Confusion	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Headache	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Encephalitis	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Abdominal pain	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Cough	1 participants	—	—	—	—	—	—	—
Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events Dyspnea	1 participants	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 4 years following completion of therapy

-The response definitions used for this study are the 2007 Cheson criteria.

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=18 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Efficacy of Treatment as Measured by Best Overall Response Progressive Disease	3 participants	—	—	—	—	—	—	—
Efficacy of Treatment as Measured by Best Overall Response Stable disease	3 participants	—	—	—	—	—	—	—
Efficacy of Treatment as Measured by Best Overall Response Partial response	9 participants	—	—	—	—	—	—	—
Efficacy of Treatment as Measured by Best Overall Response Complete response	3 participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to 4 years following completion of therapy

Population: 12 out of the 18 participants had a complete or partial response.

-The progression definitions used for this study are from the 2007 Cheson criteria.

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=18 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Time to Progression Best response of complete response	199 days Interval 190.0 to 864.0	—	—	—	—	—	—	—
Time to Progression Best response of partial response	143 days Interval 85.0 to 240.0	—	—	—	—	—	—	—
Time to Progression Best response of stable disease	88 days Interval 55.0 to 116.0	—	—	—	—	—	—	—
Time to Progression All participants	127 days Interval 23.0 to 864.0	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=12 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders n=6 Participants Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads Baseline	0.372 copies/peripheral blood mononuclear cell Standard Error 0.123	0.417 copies/peripheral blood mononuclear cell Standard Error 0.045	—	—	—	—	—	—
Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads Study completion	0.0128 copies/peripheral blood mononuclear cell Standard Error 0.023	0.033 copies/peripheral blood mononuclear cell Standard Error 0.147	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Population: Average RPKM values normalized to Patient A before therapy.

Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=1 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders n=1 Participants Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy n=1 Participants	Patient B (Responder) Post-Therapy n=1 Participants	Patient C (Non-responder) Pre-Therapy n=1 Participants	Patient C (Non-responder) Post-Therapy n=1 Participants	Patient D (Non-responder) Pre-Therapy n=1 Participants	Patient D (Non-responder) Post-Therapy n=1 Participants
Relation of NFκB Gene Expression Profile on Response CD45	1.000 fold expression Standard Error 0.000	1.718 fold expression Standard Error 0.045	2.049 fold expression Standard Error 0.035	0.959 fold expression Standard Error 0.016	1.163 fold expression Standard Error 0.021	1.640 fold expression Standard Error 0.039	0.594 fold expression Standard Error 0.008	0.714 fold expression Standard Error 0.019
Relation of NFκB Gene Expression Profile on Response BLK	1.000 fold expression Standard Error 0.000	0.178 fold expression Standard Error 0.015	0.889 fold expression Standard Error 0.150	0.172 fold expression Standard Error 0.073	68.856 fold expression Standard Error 10.543	77.590 fold expression Standard Error 12.715	233.179 fold expression Standard Error 60.619	46.801 fold expression Standard Error 13.193
Relation of NFκB Gene Expression Profile on Response CADMI	1.000 fold expression Standard Error 0.000	0.011 fold expression Standard Error 0.001	0.623 fold expression Standard Error 0.031	0.007 fold expression Standard Error 0.001	1.494 fold expression Standard Error 0.190	1.816 fold expression Standard Error 0.105	2.013 fold expression Standard Error 0.085	0.470 fold expression Standard Error 0.026
Relation of NFκB Gene Expression Profile on Response CD25	1.000 fold expression Standard Error 0.000	0.035 fold expression Standard Error 0.006	0.303 fold expression Standard Error 0.013	0.015 fold expression Standard Error 0.003	0.862 fold expression Standard Error 0.013	0.691 fold expression Standard Error 0.013	2.897 fold expression Standard Error 0.098	0.512 fold expression Standard Error 0.023
Relation of NFκB Gene Expression Profile on Response CD4	1.000 fold expression Standard Error 0.000	1.380 fold expression Standard Error 0.047	1.437 fold expression Standard Error 0.080	0.607 fold expression Standard Error 0.023	1.319 fold expression Standard Error 0.075	1.923 fold expression Standard Error 0.092	3.057 fold expression Standard Error 0.340	0.648 fold expression Standard Error 0.056

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=12 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders n=6 Participants Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA Baseline	37.0 copies/peripheral blood mononuclear cell Standard Error 11.9	41.9 copies/peripheral blood mononuclear cell Standard Error 29.1	—	—	—	—	—	—
Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA Study completion	7.33 copies/peripheral blood mononuclear cell Standard Error 2.76	35.7 copies/peripheral blood mononuclear cell Standard Error 23.7	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=18 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence Baseline	0.49 percentage of nucleotide divergence Standard Error 0.05	—	—	—	—	—	—	—
Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence Study completion	0.52 percentage of nucleotide divergence Standard Error 0.06	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	EPOCH Chemotherapy & Bortezomib n=18 Participants Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Non-responders Patients who had stable or progressive disease after treatment.	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Effects of HTLV-1 Integration Sites After Treatment Baseline	1.31 number of integration sites Standard Error 0.31	—	—	—	—	—	—	—
Effects of HTLV-1 Integration Sites After Treatment Study completion	1.00 number of integration sites Standard Error 0.22	—	—	—	—	—	—	—

Adverse Events

EPOCH Chemotherapy & Bortezomib

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure

EPOCH Chemotherapy & Bortezomib n=18 participants at risk Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.

Infections and infestations Sepsis

5.6% 1/18 • Number of events 18

Other adverse events

Measure	EPOCH Chemotherapy & Bortezomib n=18 participants at risk Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Gastrointestinal disorders Abdominal distension	11.1% 2/18
Gastrointestinal disorders Abdominal pain	11.1% 2/18
Metabolism and nutrition disorders Albumin	22.2% 4/18
Investigations Alkaline phosphtase	22.2% 4/18
Skin and subcutaneous tissue disorders Alopecia	5.6% 1/18
Metabolism and nutrition disorders Anorexia	11.1% 2/18
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18
Eye disorders Blurred vision	5.6% 1/18
Musculoskeletal and connective tissue disorders Bone pain	11.1% 2/18
General disorders Chills	5.6% 1/18
Psychiatric disorders Confusion	11.1% 2/18
Respiratory, thoracic and mediastinal disorders Congestion	5.6% 1/18
Gastrointestinal disorders Constipation	11.1% 2/18
Respiratory, thoracic and mediastinal disorders Cough	22.2% 4/18
Renal and urinary disorders Creatinine	11.1% 2/18
Metabolism and nutrition disorders Dehydration	5.6% 1/18
Eye disorders Dry eyes	5.6% 1/18
Skin and subcutaneous tissue disorders Dry skin	5.6% 1/18
Gastrointestinal disorders Dysgeusia	5.6% 1/18
Respiratory, thoracic and mediastinal disorders Dyspnea	5.6% 1/18
General disorders Edema	11.1% 2/18
Infections and infestations Encephaltis	5.6% 1/18
Musculoskeletal and connective tissue disorders Extremity pain	5.6% 1/18
General disorders Fatigue	44.4% 8/18
General disorders Fever	11.1% 2/18
Gastrointestinal disorders GI bleed/ulcers	5.6% 1/18
Nervous system disorders Headache	16.7% 3/18
Blood and lymphatic system disorders Hemoglobin	61.1% 11/18
Metabolism and nutrition disorders Hypercalcemia	16.7% 3/18
Metabolism and nutrition disorders Hyperglycemia	22.2% 4/18
Metabolism and nutrition disorders Hypernatremia	5.6% 1/18
Vascular disorders Hypertension	5.6% 1/18
Metabolism and nutrition disorders Hypertriglyceridemia	5.6% 1/18
Metabolism and nutrition disorders Hypocalcemia	11.1% 2/18
Metabolism and nutrition disorders Hypoglycemia	11.1% 2/18
Metabolism and nutrition disorders Hypokalemia	22.2% 4/18
Metabolism and nutrition disorders Hyponatremia	22.2% 4/18
Metabolism and nutrition disorders Hypophosphatemia	11.1% 2/18
Infections and infestations IV port infection	5.6% 1/18
Gastrointestinal disorders Indigestion	11.1% 2/18
Infections and infestations Infection with neutropenia	5.6% 1/18
Infections and infestations Infection without neutropenia	11.1% 2/18
Investigations Leukocytes (WBC)	44.4% 8/18
Investigations Lymphopenia	5.6% 1/18
Metabolism and nutrition disorders Magnesium	16.7% 3/18
Gastrointestinal disorders Mucositis	16.7% 3/18
Skin and subcutaneous tissue disorders Nail discoloration	5.6% 1/18
Gastrointestinal disorders Nausea	11.1% 2/18
Infections and infestations Neutropenic fever	16.7% 3/18
Investigations Neutrophils (ANC)	38.9% 7/18
Infections and infestations Omaya port infection	5.6% 1/18
Nervous system disorders Opthalmoplegia/laryngeal/aphasia	5.6% 1/18
Skin and subcutaneous tissue disorders Pigment changes	5.6% 1/18
Investigations Platelets	44.4% 8/18
Skin and subcutaneous tissue disorders Rash	5.6% 1/18
Respiratory, thoracic and mediastinal disorders Rhinorrhea	5.6% 1/18
Investigations SGOT (AST)	22.2% 4/18
Investigations SGPT (ALT)	22.2% 4/18
Nervous system disorders Seizure	5.6% 1/18
Nervous system disorders Sensory neuropathy	50.0% 9/18
Infections and infestations Sepsis	5.6% 1/18
Infections and infestations Septic arthritis	5.6% 1/18
Infections and infestations Sinusitis	5.6% 1/18
Gastrointestinal disorders Spontaneous bacterial peritonitis	5.6% 1/18
Metabolism and nutrition disorders Uric acid	5.6% 1/18
Infections and infestations Vaginal infection	5.6% 1/18
Gastrointestinal disorders Vomiting	11.1% 2/18
Investigations Weight loss	5.6% 1/18

Additional Information

Lee Ratner, M.D., Ph.D.

Washington University School of Medicine

Phone: 314-362-8836

Email: lratner@dom.wustl.edu

Results disclosure agreements

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