Ofatumumab/Methylprednisolone and Ofatumumab/Lenalidomide for Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01497496
• Collaborator: Novartis (Industry), Celgene Corporation (Industry)
• Enrollment: 29
• Location: 1
• Arm: 1
• Actual Duration (Months): 97.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The main purpose of this study is to see if the combination of ofatumumab with high dose methylprednisolone followed by additional treatment with ofatumumab and lenalidomide can help people with relapsed or refractory CLL/SLL get rid of their CLL/SLL for a long period of time. Researchers also want to find out if the combination of ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide is safe and tolerable.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma	Drug: High Dose Methylprednisolone (HDMP); Drug: Ofatumumab; Drug: Lenalidomide	Phase 2

Detailed Description

This is a phase II, single institution, and non-randomized study of patients with relapsed or refractory CLL/SLL, utilizing a two-stage trial design. The primary endpoint for this trial is the combined complete and partial response rate at 3 months (after the end of cycle 3) to the protocol therapy. Investigators anticipate this trial will have a complete response and partial response (CR+PR) rate of at least 55%.

A two-stage design is employed for this trial. The null/unacceptable CR+PR response rate is ≤35% while the anticipated true response rate to the protocol treatment is at least 55% for each disease cohort. At the first stage, 25 patients will be accrued to the trial. If 9 or fewer of these patients respond, then the trial will be terminated early and the response rate to the protocol treatment will be deemed unacceptable (≤35%). Otherwise, if more than 9 patients respond during the first stage, an additional 31 patients will be enrolled to this trial during stage 2 for a total of 56 patients. If 25 or fewer of these 56 patients respond to the protocol treatment at the end of stage 2, no further investigation of the protocol treatment is considered warranted. On the other hand, if more than 25 patients out of the 56 enrolled patients respond, the protocol treatment will be considered promising. If the true response rate is ≤35%, the probability of ending the trial at stage 1 is 0.63. If, however, the true response rate is at least 55%, then the probability of ending the trial at stage 1 is only 0.04. This two-stage design has an overall alpha level of 0.047 and a power of 0.90.

For the purpose of interim analysis at the end of stage 1, the objective response will be measured by the end of 3 months (or end of cycle 3) from the start of the protocol treatment prior to the initiation of the combination of ofatumumab with lenalidomide. The accrual will not be suspended while waiting for the results of the interim analysis unless the observed objective response rate among those patients whose objective response data are available is below 30%.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Relapsed or Refractory CLL/SLL The HiLOG Trial
• Actual Study Start Date: Jan 26, 2012
• Actual Primary Completion Date: Sep 25, 2019
• Actual Study Completion Date: Mar 20, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Immunotherapy Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab.

Drug: High Dose Methylprednisolone (HDMP); 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Other Names: HDMP corticosteroid ; Drug: Ofatumumab; Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1; Other Names: Arzerra® ; Drug: Lenalidomide; The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl); Other Names: Revlimid® IMiD® compound

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [3 Months]

   ORR at 3 months. Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. Objective response = Complete Response (disappearance of all target lesions) + Partial Response (>=30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)

Secondary Outcome Measures

1. Rate of Progression-free Survival (PFS) [36 Months]

   Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD) defined according to NCIWG 2008 CLL Criteria for Response.

2. Rate of Overall Survival (OS) [36 Months]

   Overall Survival Time: Time from initiation of treatment to time of death. Overall survival will be summarized with the Kaplan-Meier curve.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form

• Able to adhere to the study visit schedule and other protocol requirements

• Patients must have histologically or cytologically confirmed CD5+/CD20+ B-Cell chronic lymphocytic leukemia or small lymphocytic lymphoma. The diagnosis of CLL is based upon the National Comprehensive Cancer Network (NCCN) guidelines. Any outside pathology slides used as inclusion criteria for the patient will be reviewed at this institution to confirm the diagnosis. The patient must meet all of the following CLL criteria to participate in this study: absolute lymphocyte count > 5000/μL; CD20+ and CD5+; Bone marrow (BM) lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with less than 5000/μl or less than 30% lymphocytes in BM.

• Patients are eligible if they have relapsed or refractory CLL/SLL.

• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

• Laboratory test results within these ranges: Absolute neutrophil count ≥ 1000/mm³, Platelet count ≥50,000 /mm³, Renal function assessed by calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula, Total bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) ≤ 2.5 x ULN, Alkaline phosphatase <2.5 x ULN

• Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight heparin)

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form

• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)

• Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Evidence of laboratory Tumor Lysis Syndrome (TLS) by Cairo-Bishop Definition. Patients may be enrolled upon correction of electrolyte abnormalities.

• Use of any other experimental drug or therapy within 28 days of baseline

• Known hypersensitivity to thalidomide

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

• Any prior use of lenalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known seropositive for or active viral infection with human immunodeficiency virus (HIV)

• Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test will be performed and if positive the patient will be excluded. Note: If HBcAb positive and HBsAb positive, which is indicative of a past infection, the patient can be included. Patients who are seropositive because of hepatitis B virus vaccine are eligible.

• Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibodies (HCAb), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result

• Patients who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) are ineligible.

• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C

• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to randomization, congestive heart failure [New York Heart Association (NYHA) III-IV], and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities

• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Novartis
• Celgene Corporation

Investigators

• Principal Investigator: Celeste Bello, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 2, 2017

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01497496
• Other Study ID Numbers: MCC-16631; COMB157AUS08T; RV-CLL-PI-0560
• First Posted: Dec 22, 2011
• Last Update Posted: Apr 27, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: leukemia; lymphoma; consolidative therapy; combination regimen; Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Lenalidomide; Ofatumumab; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. Time of therapy: until disease progression or toxicity.
Period Title: Overall Study
STARTED	29
COMPLETED	29
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. High Dose Methylprednisolone (HDMP): 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15 Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1 Lenalidomide: The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 55.2%
>=65 years	13 44.8%
Sex: Female, Male (Count of Participants)
Female	4 13.8%
Male	25 86.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.9%
Not Hispanic or Latino	26 89.7%
Unknown or Not Reported	1 3.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	26 89.7%
More than one race	0 0%
Unknown or Not Reported	3 10.3%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR at 3 months. Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. Objective response = Complete Response (disappearance of all target lesions) + Partial Response (>=30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

Evaluable participants

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. High Dose Methylprednisolone (HDMP): 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15 Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1 Lenalidomide: The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
Measure Participants	27
Number [percentage of participants]	48.3 166.6%

2. Secondary Outcome

Title	Rate of Progression-free Survival (PFS)
Description	Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD) defined according to NCIWG 2008 CLL Criteria for Response.
Time Frame	36 Months

Outcome Measure Data

Analysis Population Description

Data not collected (likely futility from low accrual due to competing commercially available treatment)

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. High Dose Methylprednisolone (HDMP): 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15 Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1 Lenalidomide: The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
Measure Participants	0

3. Secondary Outcome

Title	Rate of Overall Survival (OS)
Description	Overall Survival Time: Time from initiation of treatment to time of death. Overall survival will be summarized with the Kaplan-Meier curve.
Time Frame	36 Months

Outcome Measure Data

Analysis Population Description

Data not collected (likely futility from low accrual due to competing commercially available treatment)

Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. High Dose Methylprednisolone (HDMP): 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15 Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1 Lenalidomide: The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
Measure Participants	0

Adverse Events

Time Frame	7 years, 6 months
Arm/Group Title	Immunotherapy
Arm/Group Description	Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab. High Dose Methylprednisolone (HDMP): 1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15 Ofatumumab: Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1 Lenalidomide: The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
All Cause Mortality
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)
Serious Adverse Events
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	25/29 (86.2%)
Blood and lymphatic system disorders
Anemia	4/29 (13.8%)	6
Febrile neutropenia	9/29 (31%)	13
Leukocytosis	2/29 (6.9%)	4
Cardiac disorders
Atrial fibrillation	1/29 (3.4%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders - Other	1/29 (3.4%)	1
Gastrointestinal disorders
Abdominal Pain	2/29 (6.9%)	2
Colitis	1/29 (3.4%)	1
Diarrhea	1/29 (3.4%)	1
Gastrointestinal disorders -Other	1/29 (3.4%)	1
Diverticulitis	1/29 (3.4%)	1
General disorders
Death	1/29 (3.4%)	1
Fatigue	3/29 (10.3%)	4
Fever	1/29 (3.4%)	1
General disorders and administrative site conditions -Other	1/29 (3.4%)	1
Multi-organ failure	1/29 (3.4%)	1
Leg pain	1/29 (3.4%)	1
Infections and infestations
Enterocolitis infectious	1/29 (3.4%)	1
Infections and infestations - Other	6/29 (20.7%)	6
Lung infection	9/29 (31%)	10
Sepsis	4/29 (13.8%)	4
Skin infection	2/29 (6.9%)	2
Upper respiratory infection	3/29 (10.3%)	4
Urinary tract infection	1/29 (3.4%)	1
Investigations
Alkaline phosphatase increased	1/29 (3.4%)	1
Aspartate aminotransferase increased	1/29 (3.4%)	1
Blood bilirubin increased	1/29 (3.4%)	2
Creatinine increased	1/29 (3.4%)	2
Neutrophil count decreased	25/29 (86.2%)	107
Platelet count decreased	8/29 (27.6%)	23
White blood cell decreased	12/29 (41.4%)	36
Metabolism and nutrition disorders
Dehydration	3/29 (10.3%)	3
Hyperglycemia	4/29 (13.8%)	8
Hyperkalemia	1/29 (3.4%)	1
Hyponatremia	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	2/29 (6.9%)	2
Nervous system disorders
Dizziness	2/29 (6.9%)	2
Psychiatric disorders
Insomnia	1/29 (3.4%)	1
Renal and urinary disorders
Renal calculi	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/29 (6.9%)	2
Penumonitis	2/29 (6.9%)	2
Vascular disorders
Hypotension	1/29 (3.4%)	1
Thromboembolic event	2/29 (6.9%)	2
Vascular disorders - Other	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Immunotherapy
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Blood and lymphatic system disorders
Anemia	6/29 (20.7%)	8
Intermittent anemia	2/29 (6.9%)	2
Blood and lymphatic system disorders - Other	1/29 (3.4%)	1
Febrile neutropenia	1/29 (3.4%)	1
Leukocytosis -leukopenia	1/29 (3.4%)	2
Intermittent Lymph node pain	1/29 (3.4%)	1
Lymph node pain - abdominal	1/29 (3.4%)	1
Lymph node pain - pain & swelling	1/29 (3.4%)	1
Cardiac disorders
Atrial fibrillation	1/29 (3.4%)	1
Cardiac disorders - Other	1/29 (3.4%)	1
Cardiac disorders - Other	1/29 (3.4%)	1
Cardiac disorders -other	2/29 (6.9%)	2
Cardiac disorders - Other	1/29 (3.4%)	1
Cardiac disorders - Other	1/29 (3.4%)	1
Palpitations	3/29 (10.3%)	3
Sinus bradycardia	2/29 (6.9%)	2
Sinus tachycardia	2/29 (6.9%)	2
Ear and labyrinth disorders
Ear pain	3/29 (10.3%)	3
Hearing impairment	1/29 (3.4%)	1
Middle ear inflammation	1/29 (3.4%)	1
Vertigo	2/29 (6.9%)	2
Endocrine disorders
Endocrine disorders Other	1/29 (3.4%)	1
Endocrine disorders - Other	1/29 (3.4%)	1
Eye disorders
Blurred vision	4/29 (13.8%)	4
visual disturbances	2/29 (6.9%)	2
Conjunctivitis	2/29 (6.9%)	2
Dry eye	2/29 (6.9%)	2
Eye disorders - Other	6/29 (20.7%)	6
Eye pain	1/29 (3.4%)	1
Keratitis	1/29 (3.4%)	3
Watering eyes	1/29 (3.4%)	1
Gastrointestinal disorders
Abdominal cramping	3/29 (10.3%)	3
Abdominal discomfort	1/29 (3.4%)	1
Abdominal pain	9/29 (31%)	10
Abdominal bloating	6/29 (20.7%)	6
Constipation	17/29 (58.6%)	21
Diarrhea	16/29 (55.2%)	31
Dry mouth	2/29 (6.9%)	2
Dyspepsia	1/29 (3.4%)	1
Dysphagia	1/29 (3.4%)	1
Flatulence	1/29 (3.4%)	1
Gastritis	1/29 (3.4%)	1
Gastrointestinal reflux disease	5/29 (17.2%)	11
Gastrointestinal disorders -Other	1/29 (3.4%)	1
Gastrointestinal disorders - Other	1/29 (3.4%)	1
Gastrointestinal disorders - Other	1/29 (3.4%)	1
Gastrointestinal disorders - Other	1/29 (3.4%)	1
Gastrointestinal pain	2/29 (6.9%)	3
Gastroparesis, mild	1/29 (3.4%)	1
Mucositis oral	3/29 (10.3%)	3
Nausea, intermittent	4/29 (13.8%)	6
Nausea	12/29 (41.4%)	13
Oral dysesthesia	1/29 (3.4%)	1
Oral pain	1/29 (3.4%)	1
Rectal hemorrhage	1/29 (3.4%)	1
Stomach pain	2/29 (6.9%)	3
Toothache	1/29 (3.4%)	1
Vomiting, intermittent	1/29 (3.4%)	1
Vomiting	8/29 (27.6%)	9
Rigors	2/29 (6.9%)	2
General disorders
Chills	10/29 (34.5%)	11
Edema, face	2/29 (6.9%)	2
Edema, limbs	12/29 (41.4%)	21
Fatigue	16/29 (55.2%)	24
Fever	12/29 (41.4%)	17
Flu like symptoms	1/29 (3.4%)	1
Gait disturbance	1/29 (3.4%)	1
Gait disturbance	1/29 (3.4%)	1
Gait disturbance	1/29 (3.4%)	1
Hemorrhoids	1/29 (3.4%)	1
Infusion related reaction	4/29 (13.8%)	4
Irritability	6/29 (20.7%)	6
Malaise	2/29 (6.9%)	2
Left hip pain	1/29 (3.4%)	1
port pain	1/29 (3.4%)	1
throat pain	1/29 (3.4%)	1
Inguinal pain, groin pain	2/29 (6.9%)	2
General disorders - Other	1/29 (3.4%)	1
Upper axilla pain	1/29 (3.4%)	1
hip pain	2/29 (6.9%)	2
General disorders - Other	1/29 (3.4%)	1
Joint pain	1/29 (3.4%)	1
Shooting pain, right leg	1/29 (3.4%)	1
Wrist pain	1/29 (3.4%)	1
Hepatobiliary disorders
Gallbladder polyps	1/29 (3.4%)	1
Immune system disorders
Allergic reaction	5/29 (17.2%)	5
Cytokine release syndrome	3/29 (10.3%)	3
Infections and infestations
Bronchial infection	2/29 (6.9%)	2
Enterocolitis infections	2/29 (6.9%)	2
Infections and Infestations - Other	4/29 (13.8%)	5
Lung infection	3/29 (10.3%)	3
Pharyngitis	1/29 (3.4%)	1
Rhinitis ineffective	2/29 (6.9%)	2
Sinusitis	4/29 (13.8%)	4
Skin infection	3/29 (10.3%)	5
Upper respiratory infection	7/29 (24.1%)	13
Urinary tract infection	3/29 (10.3%)	3
Injury, poisoning and procedural complications
Bruising	7/29 (24.1%)	7
Fall	2/29 (6.9%)	2
Injury, poisoning and procedural complications - Other	3/29 (10.3%)	3
Papular lesion on face	1/29 (3.4%)	1
Investigations
alamine aminotransferase increased	5/29 (17.2%)	10
Alkaline phosphatase increased	5/29 (17.2%)	12
Aspartate aminotransferase increased	3/29 (10.3%)	4
Blood bilirubin increased	3/29 (10.3%)	3
Creatinine increased	5/29 (17.2%)	7
Investigations - Other	5/29 (17.2%)	5
Lymphocyte count increased	1/29 (3.4%)	1
Neutrophil count decreased	22/29 (75.9%)	94
Platelet count decreased	11/29 (37.9%)	26
Weight loss	4/29 (13.8%)	5
White blood cell decreased	22/29 (75.9%)	115
Metabolism and nutrition disorders
Anorexia	9/29 (31%)	12
Dehydration	1/29 (3.4%)	1
Hypercalcemia	3/29 (10.3%)	3
Hyperglycemia	17/29 (58.6%)	34
Hyperkalemia	5/29 (17.2%)	6
Hyperuricemia	2/29 (6.9%)	2
Hypoalbuminemia	4/29 (13.8%)	6
Hypocalcemia	1/29 (3.4%)	1
Hypoglycemia	2/29 (6.9%)	2
Hypokalemia	2/29 (6.9%)	2
Hypomagnesemia	3/29 (10.3%)	4
Hyponatremia	4/29 (13.8%)	6
Iron overload	1/29 (3.4%)	1
Metabolism and nutrition disorders - Other	10/29 (34.5%)	33
Musculoskeletal and connective tissue disorders
Bone pain	1/29 (3.4%)	1
Muscle pain	2/29 (6.9%)	2
Arthralgia	1/29 (3.4%)	3
Back pain	4/29 (13.8%)	5
Buttock pain	1/29 (3.4%)	1
Generalized muscle weakness	7/29 (24.1%)	7
Muscle weakness, lower limb	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorder - Other	4/29 (13.8%)	4
Myalgia	5/29 (17.2%)	5
Neck pain	5/29 (17.2%)	5
Pain in extremity	4/29 (13.8%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified -Other	2/29 (6.9%)	2
Tumor pain	8/29 (27.6%)	11
Nervous system disorders
Akathisia	2/29 (6.9%)	5
Ataxia	1/29 (3.4%)	1
Concentration impairment	3/29 (10.3%)	3
Dizziness	10/29 (34.5%)	15
Dysgeusia	4/29 (13.8%)	5
Headache	7/29 (24.1%)	14
Memory impairment	2/29 (6.9%)	2
Movement, involuntary	9/29 (31%)	10
Nervous system disorders - Other	4/29 (13.8%)	4
Parasthesia	1/29 (3.4%)	2
Peripheral sensory neuropathy	15/29 (51.7%)	21
Tremor	7/29 (24.1%)	7
Psychiatric disorders
Agitation	6/29 (20.7%)	7
Anxiety	2/29 (6.9%)	2
Confusion	1/29 (3.4%)	1
Depression	3/29 (10.3%)	4
Insomnia	13/29 (44.8%)	13
Personality change	1/29 (3.4%)	1
Renal and urinary disorders
Acute kidney injury	2/29 (6.9%)	2
Hematuria	1/29 (3.4%)	1
Renal and urinary disorders - Other	1/29 (3.4%)	1
Urinary frequency	10/29 (34.5%)	11
Urinary incontinence	1/29 (3.4%)	1
Urinary urgency	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	8/29 (27.6%)	9
Cough	10/29 (34.5%)	18
Dyspnea	13/29 (44.8%)	17
Epistaxis	2/29 (6.9%)	2
Hiccups	2/29 (6.9%)	4
Hoarseness	6/29 (20.7%)	6
Hypoxia	1/29 (3.4%)	1
Nasal congestion	5/29 (17.2%)	5
Pleural effusion	1/29 (3.4%)	1
Pneumonia	1/29 (3.4%)	1
Post nasal drip	2/29 (6.9%)	2
Productive cough	7/29 (24.1%)	8
Reespiratory, thoracic and mediastinal disorders - Other	1/29 (3.4%)	1
Sleep apnea	1/29 (3.4%)	1
Sore throat	6/29 (20.7%)	6
Skin and subcutaneous tissue disorders
Alopecia	1/29 (3.4%)	2
Dry skin	3/29 (10.3%)	4
Erythema multiforme	4/29 (13.8%)	4
Erythroderma	1/29 (3.4%)	1
Hyperhidrosis	15/29 (51.7%)	16
Hypertrichosis	1/29 (3.4%)	1
Hypohidrosis	2/29 (6.9%)	2
Pain of skin	1/29 (3.4%)	1
Photosensitivity	1/29 (3.4%)	1
Pruritus	9/29 (31%)	12
Rash maculo-papular	6/29 (20.7%)	11
Skin and subcutaneous tissue disorders - Other	11/29 (37.9%)	16
Skin hyperpigmentation	4/29 (13.8%)	4
Skin ulceration	2/29 (6.9%)	2
Surgical and medical procedures
Surgical and medical procedures - Other	4/29 (13.8%)	9
Vascular disorders
Flushing	2/29 (6.9%)	2
Hypertension	3/29 (10.3%)	8
Hypotension	4/29 (13.8%)	4
Vascular disorders - Other	1/29 (3.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.