Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)

• Sponsor: David Rizzieri, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01373229
• Collaborator: Celgene Corporation (Industry), Genzyme, a Sanofi Company (Industry)
• Enrollment: 21
• Location: 1
• Arm: 1
• Actual Duration (Months): 37.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.

The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Lymphocytic, Chronic, B-Cell	Drug: Lenalidomide + Plerixafor (+ Rituximab)	Phase 1

Detailed Description

The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."

Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is <100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:

• Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)

• Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)

• Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)

• Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.

An interim assessment of response will be performed after 4 cycles of combination therapy:

• Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.

• Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.

• Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lenalidomide in Combination With Plerixafor in Patients With Previously Treated Chronic Lymphocytic Leukemia
• Actual Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lenalidomide + Plerixafor+ Rituximab Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Cohort 3: 0.42 mg/kg Cohort 4: 0.54 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.

Drug: Lenalidomide + Plerixafor (+ Rituximab); Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Cohort 3: 0.42 mg/kg Cohort 4: 0.54 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.; Other Names: Revlimid Mozobil Rituxan

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose [4-16 months]

Secondary Outcome Measures

1. Overall Response (Complete Response/Partial Response) [at the end of 4 months of combination treatment and at 2 months after completion of therapy]

   NCI 96 Response Criteria CR (Complete Response): Lymphadenopathy = none > 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = <4000 per microliter Marrow = normocellular, <30% lymphocytes, no B-lymphoid nodules. Platelet count = >100,000 per microliter Hemoglobin = >11.0 grams per deciliter Neutrophils = >1500 per microliter PR (Partial Response): Lymphadenopathy = Decrease >/= 50% Hepatomegaly = Decrease >/= 50% Splenomegaly = Decrease >/= 50% Blood lymphocytes = Decrease >/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = >100,000 per microliter or increase >/= 50% over baseline Hemoglobin = >11.0 grams per deciliter or increase >/= 50% over baseline Neutrophils = >1500 per microliter or increase >/= 50% over baseline

2. Progression-free Survival (PFS) [time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first]

3. Overall Survival (OS) [the time from day 1 of treatment to death or 2 years, whichever comes first]

4. Reduction in Severity of B Symptoms [at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy]

   Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.

5. Reduction in the Frequency of Blood and Platelet Transfusions [4 weeks prior to therapy and in the 4 weeks following the completion of therapy]

   The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed diagnosis of chronic lymphocytic leukemia (CLL) or Small lymphocytic lymphoma (SLL) as established by the National Cancer Institute (NCI) Working Group Response Criteria (NCI 96 Criteria).

• Received one or more prior therapies for CLL.

• Subjects must have symptomatic disease requiring therapy as defined by the protocol.

• /= 4 weeks from prior cancer therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.

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

Exclusion Criteria:

• Prolymphocytic leukemia (PLL).

• Richter's (large cell) transformation.

• Prior allogeneic transplant within 12 months or prior allogeneic transplant > 12 months currently receiving immunosuppressants.

• Active autoimmune hemolytic anemia.

• Central nervous system (CNS) involvement.

• Chronic enteral corticosteroids > 10mg prednisone or equivalent.

• Evidence of laboratory tumor lysis syndrome (TLS) by Cairo-Bishop Definition of Tumor Lysis Syndrome

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

• Major surgery 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.

• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• David Rizzieri, MD
• Celgene Corporation
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: David A Rizzieri, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Rizzieri, MD, Associate Professor of Medicine, Duke University
• ClinicalTrials.gov Identifier: NCT01373229
• Other Study ID Numbers: Pro00026715; RV0622
• First Posted: Jun 14, 2011
• Last Update Posted: Feb 5, 2018
• Last Verified: Jul 1, 2017

• Keywords provided by David Rizzieri, MD, Associate Professor of Medicine, Duke University: Chronic Lymphocytic Leukemia; CLL
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Plerixafor; Rituximab; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from the CLL clinic at Duke Medical Center from January 2012 to December 2013.
Pre-assignment Detail	21 subjects were consented to this study. Six (6) were screen failures; therefore, only 15 subjects began the treatment regimen which included a lenalidomide run-in phase. Three (3) subjects were unable to complete the run-in phase. Three (3) subjects died prior to completing stage 2, and so were not evaluable for DLT.

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Period Title: Overall Study
STARTED	15
COMPLETED	9
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 73.3%
>=65 years	4 26.7%
Sex: Female, Male (Count of Participants)
Female	4 26.7%
Male	11 73.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	15 100%
Unknown or Not Reported	0 0%
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	1 6.7%
White	14 93.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose
Time Frame	4-16 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	9
Number [mg/kg]	0.24

2. Secondary Outcome

Title	Overall Response (Complete Response/Partial Response)
Description	NCI 96 Response Criteria CR (Complete Response): Lymphadenopathy = none > 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = <4000 per microliter Marrow = normocellular, <30% lymphocytes, no B-lymphoid nodules. Platelet count = >100,000 per microliter Hemoglobin = >11.0 grams per deciliter Neutrophils = >1500 per microliter PR (Partial Response): Lymphadenopathy = Decrease >/= 50% Hepatomegaly = Decrease >/= 50% Splenomegaly = Decrease >/= 50% Blood lymphocytes = Decrease >/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = >100,000 per microliter or increase >/= 50% over baseline Hemoglobin = >11.0 grams per deciliter or increase >/= 50% over baseline Neutrophils = >1500 per microliter or increase >/= 50% over baseline
Time Frame	at the end of 4 months of combination treatment and at 2 months after completion of therapy

Outcome Measure Data

Analysis Population Description

Three (3) subjects were unable to complete the run-in phase. Three (3) subjects died prior to completing stage 2, and three (3) subjects were unable to complete 4 cycles of combination therapy. Therefore, only 6 subjects were analyzed for response.

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	6
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Time Frame	time from day 1 of treatment to disease progression, death, or 2 years, whichever comes first

Outcome Measure Data

Analysis Population Description

Subjects who experienced disease progression

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	3
Mean (Standard Deviation) [months]	11 (1)

4. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	the time from day 1 of treatment to death or 2 years, whichever comes first

Outcome Measure Data

Analysis Population Description

Subjects who died on study

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	8
Mean (Standard Deviation) [months]	5.5 (10)

5. Secondary Outcome

Title	Reduction in Severity of B Symptoms
Description	Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.
Time Frame	at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapy

Outcome Measure Data

Analysis Population Description

Data were not collected and the Outcome will never be analyzed

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	0

6. Secondary Outcome

Title	Reduction in the Frequency of Blood and Platelet Transfusions
Description	The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.
Time Frame	4 weeks prior to therapy and in the 4 weeks following the completion of therapy

Outcome Measure Data

Analysis Population Description

Data were not collected and the Outcome will never be analyzed

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
Measure Participants	0

Adverse Events

Arm/Group Title	Lenalidomide + Plerixafor+ Rituximab
Arm/Group Description	Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) <100.0 x 109 / L. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide: Cohort 1: 0.24 mg/kg Cohort 2: 0.32 mg/kg Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR. Subjects will then continue single agent lenalidomide until disease progression.
All Cause Mortality
	Lenalidomide + Plerixafor+ Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lenalidomide + Plerixafor+ Rituximab
	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)
Blood and lymphatic system disorders
Anemia	1/15 (6.7%)	1
Febrile neutropenia	2/15 (13.3%)	2
Hemolysis	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	1
General disorders
Death NOS	1/15 (6.7%)	1
Fever	1/15 (6.7%)	1
Infections and infestations
Infections and infestations - Other, specify	1/15 (6.7%)	1
Sepsis	2/15 (13.3%)	2
Investigations
Platelet count decreased	1/15 (6.7%)	1
White blood cell decreased	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/15 (6.7%)	1
Nervous system disorders
Dysphasia	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/15 (20%)	3
Vascular disorders
Hypotension	1/15 (6.7%)	1
Thromboembolic event	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Lenalidomide + Plerixafor+ Rituximab
	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)
Blood and lymphatic system disorders
Anemia	13/15 (86.7%)	14
Blood and lymphatic system disorders - Other, specify	1/15 (6.7%)	2
Lymph node pain	1/15 (6.7%)	1
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	1/15 (6.7%)	1
Hearing impaired	1/15 (6.7%)	1
Eye disorders
Blurred vision	1/15 (6.7%)	1
Dry eye	1/15 (6.7%)	1
Eye disorders - Other, specify	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	1
Anal ulcer	1/15 (6.7%)	1
Constipation	3/15 (20%)	3
Diarrhea	4/15 (26.7%)	6
Dry mouth	3/15 (20%)	3
Dyspepsia	1/15 (6.7%)	2
Flatulence	1/15 (6.7%)	1
Gastrointestinal disorders - Other, specify	3/15 (20%)	3
Nausea	5/15 (33.3%)	5
Stomach pain	1/15 (6.7%)	1
Vomiting	1/15 (6.7%)	1
General disorders
Chills	1/15 (6.7%)	1
Edema limbs	5/15 (33.3%)	5
Fatigue	9/15 (60%)	12
Fever	3/15 (20%)	4
General disorders and administration site conditions - Other, specify	4/15 (26.7%)	5
Pain	3/15 (20%)	3
Immune system disorders
Allergic reaction	1/15 (6.7%)	1
Cytokine release syndrome	1/15 (6.7%)	1
Infections and infestations
Infections and infestations - Other, specify	1/15 (6.7%)	1
Sinusitis	4/15 (26.7%)	4
Skin infection	1/15 (6.7%)	1
Investigations
Creatinine increased	2/15 (13.3%)	2
Neutrophil count decreased	13/15 (86.7%)	27
Platelet count decreased	11/15 (73.3%)	16
Weight loss	2/15 (13.3%)	2
Metabolism and nutrition disorders
Anorexia	7/15 (46.7%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	2/15 (13.3%)	2
Back pain	2/15 (13.3%)	2
Chest wall pain	1/15 (6.7%)	1
Generalized muscle weakness	2/15 (13.3%)	2
Joint range of motion decreased	1/15 (6.7%)	1
Myalgia	1/15 (6.7%)	1
Nervous system disorders
Concentration impairment	1/15 (6.7%)	1
Dysgeusia	1/15 (6.7%)	1
Extrapyramidal disorder	1/15 (6.7%)	1
Headache	2/15 (13.3%)	2
Paresthesia	1/15 (6.7%)	2
Psychiatric disorders
Agitation	1/15 (6.7%)	1
Depression	1/15 (6.7%)	1
Insomnia	2/15 (13.3%)	2
Renal and urinary disorders
Urinary frequency	2/15 (13.3%)	4
Urinary urgency	1/15 (6.7%)	1
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	7/15 (46.7%)	7
Dyspnea	4/15 (26.7%)	4
Hoarseness	1/15 (6.7%)	1
Nasal congestion	5/15 (33.3%)	6
Respiratory, thoracic and mediastinal disorders - Other, specify	2/15 (13.3%)	2
Skin and subcutaneous tissue disorders
Dry skin	1/15 (6.7%)	1
Pruritus	2/15 (13.3%)	2
Rash maculo-papular	3/15 (20%)	4
Skin and subcutaneous tissue disorders - Other, specify	1/15 (6.7%)	2
Vascular disorders
Hot flashes	3/15 (20%)	3
Hypotension	1/15 (6.7%)	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.