Trial Outcomes & Findings for Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome (NCT NCT00466921)

NCT ID: NCT00466921

Last Updated: 2020-12-01

Results Overview

In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following: CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (\< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal. PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (\<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: After cycle 4 of treatment (1 cycle =28 days)
• Results posted on: 2020-12-01

Participant Flow

The study opened February 24, 2004 to accrual with the first patient being treated on study April 19 2005. the study closed to further accrual February 7, 2011 after the last patient initiated study treatment.

Participant milestones

Measure	Lenalidomide lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
First 3 Cycles of Treatment STARTED	33
First 3 Cycles of Treatment Completed 1 Cycle	32
First 3 Cycles of Treatment Started Cycle 2	31
First 3 Cycles of Treatment Completed 3 Cycles	26
First 3 Cycles of Treatment COMPLETED	26
First 3 Cycles of Treatment NOT COMPLETED	7
Completed 4 Cycles/Reached 1st Response STARTED	26
Completed 4 Cycles/Reached 1st Response Completed 4 Cycles/1st Response	21
Completed 4 Cycles/Reached 1st Response COMPLETED	21
Completed 4 Cycles/Reached 1st Response NOT COMPLETED	5
Continued Treatment STARTED	21
Continued Treatment COMPLETED	21
Continued Treatment NOT COMPLETED	0
Follow up for a Minimum of 1 Year STARTED	33
Follow up for a Minimum of 1 Year COMPLETED	27
Follow up for a Minimum of 1 Year NOT COMPLETED	6

Reasons for withdrawal

Measure	Lenalidomide lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
First 3 Cycles of Treatment Adverse Event	2
First 3 Cycles of Treatment Withdrawal by Subject	5
Completed 4 Cycles/Reached 1st Response Withdrawal by Subject	2
Completed 4 Cycles/Reached 1st Response Progressive Disease	2
Completed 4 Cycles/Reached 1st Response Other	1
Follow up for a Minimum of 1 Year Death	6

Baseline Characteristics

Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome

Baseline characteristics by cohort

Measure	Lenalidomide n=33 Participants lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 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	6 Participants n=5 Participants
Race (NIH/OMB) White	27 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	33 participants n=5 Participants

PRIMARY outcome

Timeframe: After cycle 4 of treatment (1 cycle =28 days)

Population: Patients considered not evaluable if they did not complete 1 cycle or were not evaluated for response

In general response to treatment is defined as either complete response (CR) or partial response (PR) assessed using Composite Assessment (CA) of index lesion disease severity and is defined as the following:

CR =CA ratio=0/no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (< 5% Sézary cells=not significant). Skin biopsy is required for documentation of CR. Confirmatory CT scans are required, if baseline CTs were abnormal.

PR= CA ratio ≥0.5/no new clinically abnormal lymph nodes/no progression of existing clinically abnormal lymph nodes (<25%)/no new cutaneous tumors/no new pathologically positive lymph nodes or visceral disease in an area previously documented as-ve for at least 4 weeks. In patients with circulating Sézary cells at least a 50% reduction of malignant lymphocytes is required.

Outcome measures

Measure	Lenalidomide n=29 Participants lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Response to Treatment CR	0 participants
Response to Treatment PR	9 participants

PRIMARY outcome

Timeframe: From time of treatment initiation until progression or death from any cause (up to a possible maximum of approximately 6 years)

PFS is defined from the time of treatment initiation until documentation of progressive disease or death from any cause.

Progressive disease is defined as (PD) ≥25% increase in CA ratio, ≥25% increase in no. or area of clinically abnormal lymph nodes/new tumors/new pathologically positive lymph nodes/visceral disease/an increase >25% in no. of Sézary cells.

Outcome measures

Measure	Lenalidomide n=32 Participants lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Progression-free Survival (PFS)	8 months Interval 3.7 to 26.1

PRIMARY outcome

Timeframe: From time of initial response until progressive disease (up to approximately 1 year)

DOR is defined as time of initial documentation of response to the time of documentation of progression in patients who achieve either a complete response (CR) and partial response (PR)

Outcome measures

Measure	Lenalidomide n=9 Participants lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Duration of Response (DOR)	10 months Interval 1.1 to 11.0

SECONDARY outcome

Timeframe: From treatment initiation until up to 30 days post treatment with possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of treatment permitted if meeting response criteria

Toxicity is defined as the number of patients who patients who experienced an adverse event that was determined to be at least possibly related to study drug and determined to be a grade 3 or higher in severity as assessed by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE) where generally:

Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Outcome measures

Measure	Lenalidomide n=33 Participants lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 Fatigue (grade 3)	7 patients
Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 Infection (grade 3)	1 patients
Number of Patients Who Experience Toxicity as Assessed by NCI CTCAE v3.0 Leukopenia (grade 3)	1 patients

OTHER_PRE_SPECIFIED outcome

Timeframe: After all patients have completed thru day 15 of course 1.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: After all patients have completed 1 course

Outcome measures

Outcome data not reported

Adverse Events

Lenalidomide

Serious events: 10 serious events

Other events: 33 other events

Deaths: 18 deaths

Serious adverse events

Measure	Lenalidomide n=33 participants at risk lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
Infections and infestations Pneumonia	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pogression of disease	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Infections and infestations Infection	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death more than 30 days from last dose of study drug	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Death dues to acute disseminated encephalomielitis	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Edema	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Mental Status Changes (PVD)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Infections and infestations Leg infection (cellulitis)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.

Other adverse events

Measure	Lenalidomide n=33 participants at risk lenalidomide: 25 mg daily orally administered on days 1 - 21 followed by 7 days rest of a 28-day cycle, or starting dose of 10mg increasing dose by 5 mg every cycle, up to a maximum of 25 mg.
General disorders Allergic rhinitis (including sneezing,nasal stuffiness,postnasal drip)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Hemoglobin (anemia)	42.4% 14/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Neutrophils (neutropenia)	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Leukocytes (total WBC)	27.3% 9/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Increased white blood cells	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Platelets (thrombocytopenia)	15.2% 5/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Cardiac disorders Hypotension	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Fatigue	69.7% 23/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Fever	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Chills	18.2% 6/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Sweating	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Weight loss	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Insomnia	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Cold intolerance	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders Weight gain	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Injection site reaction/extravasation changes	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Pruritus/itching	57.6% 19/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders erythoderma	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Rash	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Burning	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Skin peeling	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Dry skin	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Scaling	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Alopecia	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Skin and subcutaneous tissue disorders Skin ulcer	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Endocrine disorders Hot flashes/flushes	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Endocrine disorders Thyroid function, high (hyperthyroidism)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Anorexia	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Constipation	21.2% 7/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Diarrhea	27.3% 9/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Heartburn/dyspepsia	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Nausea	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders dry mouth	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Taste alteration(dysgeusia)	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Vomiting	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Inflammatory bowel disease	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Gastrointestinal disorders Abdominal bloating	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Infections and infestations Lung (pneumonia)	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Infections and infestations Infection (NOS)	24.2% 8/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Edema	15.2% 5/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Blood and lymphatic system disorders Edema extremities	39.4% 13/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Alkaline phosphatase	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Transaminase	15.2% 5/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	30.3% 10/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Creatinine Increased	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Metabolism and nutrition disorders Potassium, serum-low(hypokalemia)	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Neurosensory	15.2% 5/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Neuromotor	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Slurred speech	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Speech impairment	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Tremor	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Ataxia	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Confusion	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Psychiatric disorders Dizziness	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Psychiatric disorders Mood alteration - Depression	12.1% 4/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Muscle aches	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Muscle cramps	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Joint Stiffness	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Joint aches	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders muscle weakness	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Nervous system disorders Headache	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
General disorders GENERAL- Pain	36.4% 12/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Musculoskeletal and connective tissue disorders Pain in hands	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Respiratory, thoracic and mediastinal disorders Cough	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	9.1% 3/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Respiratory, thoracic and mediastinal disorders Dyspnea on exertion	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Eye disorders Visual	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Renal and urinary disorders Renal insufficiency	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Injury, poisoning and procedural complications fratured coccyx	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor flare - skin lesions	6.1% 2/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.
Endocrine disorders hypothyroid	3.0% 1/33 • Patients were assessed for adverse events from the time of treatment initiation until treatment discontinuation and up to 30 days post last treatment. Patients received a possible 4 cycles of initial treatment (1 cycle =28 days) and up to 2 further years of permitted treatment if meeting response criteria.

Additional Information

Clinical Trials Office

Northwestern University

Phone: 312-695-1301

Results disclosure agreements

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