Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00294632
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 54
• Location: 1
• Arm: 1
• Duration (Months): 120
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of the drug lenalidomide (Revlimid, lenalidomide) that can be given with Rituxan® (rituximab) in the treatment of relapsed mantle cell lymphoma. The safety and effectiveness of this combination treatment will also be studied in both mantle cell lymphoma and diffuse large B-cell non-Hodgkin's lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Lenalidomide; Drug: Rituximab	Phase 1/Phase 2

Detailed Description

Rituximab is a type of drug known as a monoclonal antibody. It is designed to act against the cluster of differentiation antigen 20 (CD20) antigen that is found on the surface of both normal B lymphocytes or on the malignant lymphoma cells. When rituximab attacks the CD20 antigen, it can kill the lymphoma cells. lenalidomide is known as an immunomodulatory drug. It is thought to work by helping the immune system fight disease.

If you are found to be eligible, you will receive lenalidomide plus rituximab. This study will be done in 2 phases. In the Phase I portion of this study, 6 dose levels of lenalidomide will be studied. The same level of rituximab will be given to all participants. Between 3-6 participants will be treated at each dose level. Those enrolled first on this study will receive the lowest dose of lenalidomide plus rituximab. After treatment, each dose level of lenalidomide will be evaluated to check for any intolerable side effects. The dose of lenalidomide that you will receive will depend on the time that you enter this study and the side effects of those participants that entered the study before you. Once a dose has been assigned to you, it will not increase, but it could decrease or remain the same for a while if you have intolerable side effects. Once the highest tolerable dose of lenalidomide has been found, additional participants will receive that dose during the Phase II portion of this study.

You should swallow lenalidomide capsules whole by mouth every day at the same time, with a glass of water on either a full or an empty stomach. Do not break, chew or open the capsules. This will continue for 21 days, followed by a 7-day rest period. Each 28-day period is called a cycle of therapy.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).

During Cycle 1 only, you will also take rituximab by vein once a week for 4 weeks (total of 4 doses). The first rituximab infusion (by vein) usually takes 6 to 8 hours. Later infusions are generally shorter, taking about 4 hours to complete. For participants who have a large mass or who have lymphoma cells in their blood, the rituximab dose may be split into a 2-day infusion. Vital signs (temperature, blood pressure, respiration, and heart rate) will be monitored just before, during, and after the infusions. There will be an observation period of about 1 hour after the end of each rituximab infusion, after which you will be allowed to go home.

You will be given a diary to record when you take all of the study medications and any problems or illnesses you experience. You should also write down in the diary any other medications you take while you are on this study.

After you begin your treatment on the study drug, you will have check-up visits weekly for the first cycle, every 2 weeks for Cycles 2 and 3 of therapy, and then once a month for the rest of the study. If your doctor feels it is necessary, the check-up visits may take place more often. At the end of each 28-day treatment cycle, you will have a visit with the study doctor to see if it is safe for you to continue on this study and make sure the cancer has not gotten worse. If at the end of the each cycle, your doctor believes that you are eligible to continue (based on the degree and type of side effects you are having and the response of the cancer to the study drug), you will receive enough study drug for another 28-day treatment cycle.

At these visits you will have a complete physical exam, including measurement of vital signs. You will be asked questions about how you have felt since your last visit. All medications you have taken since your last visit will be reviewed by the study doctor. You should bring the empty pill packages and any unused medication along with the diary you were given earlier to each visit. You will have a blood sample collected (around 8 tablespoons) for routine blood tests to check on the status of the disease.

If you are eligible to continue on this study, a new 28-day supply of lenalidomide capsules will be given to you at this visit. Other tests may be done at these visits to check on the status of the disease. You may have a sample of bone marrow collected and/or have either x-rays or CT scans, positron emission tomography (PET) scan (if needed), and gastrointestinal endoscopy (for patients with known or suspected site of disease) to evaluate your response to therapy. These tests may not be done at every check-up visit. They will be done when your doctor feels they are necessary. You may have unscheduled visits at any time during this study if your doctor feels it is necessary for your care.

You may continue to receive treatment as long as the cancer does not get worse and you do not experience any intolerable side effects. If, at any time during treatment, the disease gets worse or you experience any intolerable side effects, you will be taken off this study, and your doctor will discuss other treatment options with you. The number of weeks you are on the study drug depends on how well you are tolerating the study drug and how well the lymphoma responds to the study drugs.

After your participation in this study ends, and if you have completed cycle 1 or more, you will have an end-of-study visit. At this visit you will have a complete physical exam, including measurement of vital signs and weight. You will have an ECG and you will be asked questions about how you have felt since your last visit. All medications you have taken since your last visit will be reviewed by the study doctor. You will have a blood sample collected (around 3 tablespoons) for routine blood tests to check on the status of the disease. You will have bone marrow collected for tests and have either x-rays or CT scans of your body to check on the status of the disease. You should return all empty drug packaging as well as any unused lenalidomide capsules at this visit.

If you completed at least 12 and no more than 24 cycles of treatment with lenalidomide, you will have follow-up visits every 3 months. If you complete 24 or more cycles of treatment with lenalidomide, you will have follow-up visits every 6 months. This will continue until the disease gets worse. At each visit, blood (about 1 teaspoon) will be drawn to test your thyroid function. The status of your disease will be evaluated and you may have a bone marrow biopsy and aspirate. You will have a chest x-ray and CT scans of the chest, abdomen, and pelvis. If needed, you will also have a CT scan of the neck. If needed, you will have a colonoscopy or endoscopy. You may also have a bone marrow biopsy and aspirate performed.

After the end-of-study visit, you will be contacted by phone every 6 months until March 15, 2015, to check on your health and for information about any other cancer treatments you may have received.

This is an investigational study. Lenalidomide is FDA approved and commercially available. Lenalidomide is approved for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes associated with the chromosome 5 abnormality with or without other chromosome abnormalities. Lenalidomide is also approved in combination with dexamethasone for the treatment of patients with multiple myeloma that have received at least one prior therapy. Its use in this study, for relapsed mantle cell lymphoma or large B-cell Non-Hodgkin's lymphoma, is investigational. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental.

Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin's lymphomas.

Up to 71 participants with mantle cell lymphoma and 41 participants with diffuse large B-cell non-Hodgkin's lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma) will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Lenalidomide and Rituximab Treatment of Relapsed Mantle Cell Lymphoma and Diffuse Large B-Cell Non-Hodgkin's Lymphoma, Transformed Large Cell Lymphoma, and/or Grade 3 Follicular Lymphoma (Follicular Cleaved Large Cell Lymphoma or Follicular Non-Cleaved Large Cell Lymphoma (RV-LYM-PI-0056)
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Feb 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide + Rituximab Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks	Drug: Lenalidomide; Starting Dose 10 mg By Mouth Daily on Days 1-21; Other Names: CC-5013 Revlimid™ ; Drug: Rituximab; 375 mg/m^2 By Vein Weekly for 4 Weeks; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab [28 days of cycle 1]

   MTD is defined as the highest dose level in which 1 or fewer participants experienced a dose limiting toxicity (DLT) in 6 participants treated. DLT is any grade III or IV toxicity during the first 28 days (first cycle) of therapy.

Secondary Outcome Measures

1. Response of Participants Treated at Lenalidomide 20 mg [56 days, assessed after 2 cycles]

   Response definitions for measurable disease from the International Workshop Standardized Response Criteria for non-Hodgkin's Lymphoma: Complete Response (CR): Disappearance of all clinical evidence of active tumor for a minimum of four weeks. Partial Response (PR): =/>50% decrease in sum of products of all measured lesions persisting for >four weeks. No lesion may increase in size & no new lesion may appear. Minor Response (MR): >25% but less than 50% response. Stable Disease: Steady state or response less than minor & no progression for at least 8 weeks. There may be no appearance of significant new lesions. Progressive Disease: Unequivocal increase in size of any measurable lesion or appearance of significant new.

2. Objective Response Rate of Participants Treated With Lenalidomide 20 mg: Overall Response as % of Participants With Complete or Partial Response [56 days]

   Objective response rate defined as percentage of participants with complete or partial response after 2 cycles of therapy maintained for one month. Objective response monitored using Simon's optimal 2-stage design.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Phase I and Phase II: Confirmed diagnosis of mantle cell lymphoma with CD20 positivity in tissue biopsy. Patients must have previously treated relapsed and/or refractory MCL. Or for Phase II: Confirmed diagnosis of previously treated relapsed and/or refractory diffuse large B-cell lymphoma, transformed large cell lymphoma, and/or Grade 3 follicular lymphoma (follicular cleaved large cell lymphoma or follicular non-cleaved large cell lymphoma).

2. Understand and voluntarily sign an Institutional Review Board (IRB) approved informed consent form.

3. Age equal to or greater than 18 years at the time of signing the informed consent.

4. Patients must have bi-dimensional measurable disease (bone marrow only involvement is acceptable).

5. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.

6. Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl; platelet count

75,000/mm^{3 and absolute neutrophil count (ANC) > 1,000/mm}3. AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present.

1. Disease free of prior malignancies of equal to or greater than 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years.

2. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test 10-14 days prior to therapy and repeated within 24 hours of starting study drug and must either commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide.

3. Continuation from # 8 : (HIGHLY EFFECTIVE METHODS - Intrauterine device (IUD), hormonal (birth control pills, injections, implants), tubal ligation, partner's vasectomy. ADDITIONAL EFFECTIVE METHOD-latex condom, diaphragm, cervical cap) while on study drug.

4. WCBP must agree to have pregnancy tests every week for the first 4 weeks of treatment, then every 4 weeks if her menstrual cycles are regular or every 2 weeks if her cycles are irregular, while on study drug, and 4 weeks after the last dose of study drug. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.

5. Patients may have 1 to 4 lines of prior therapy for MCL (projected median 2 prior lines of therapy). Patient may or may not have received an anthracycline-based chemotherapy regimen.

6. Patients must be willing to receive transfusions of blood products.

7. Past stem cell (autologous or allogenic) transplantation is acceptable.

8. Patients may have prior therapy with rituximab.

Exclusion Criteria:

1. Any serious medical condition including but not limited to, uncontrolled hypertension, diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active infection, active hemorrhage, laboratory abnormality, or psychiatric illness that places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. Patients with history of cardiac arrythmias should have cardiac evaluation and clearance.

2. Pregnant or lactating females.

3. Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment.

4. Known hypersensitivity to thalidomide or rituximab; including the development of erythema nodosum if characterized by a desquamating rash while taking thalidomide.

5. Prior use of lenalidomide.

6. Known HIV infection. Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; not including patients with positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation.

7. All patients with history of central nervous system lymphoma.

8. Patients with peripheral blood involvement with white blood cell count (WBC) > 20,000 are EXCLUDED for the Phase I component of the study.

9. Patients with >/= Grade 3 neuropathy.

10. Patients with active pulmonary embolism or deep vein thrombosis (30 days within diagnosis).

11. Patients with severe bradycardia (heart rate <40 bpm, hypotension, light-headedness, syncope).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Celgene Corporation

Investigators

• Principal Investigator: Michael Wang, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00294632
• Other Study ID Numbers: 2005-0461; NCI-2012-01356
• First Posted: Feb 22, 2006
• Last Update Posted: Feb 24, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Mantle Cell Lymphoma; B-Cell Non-Hodgkin's Lymphoma; Transformed Large Cell Lymphoma; Follicular Lymphoma; Lymphoma; MCL; Lenalidomide; CC-5013; Revlimid™; Rituximab; Rituxan
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Rituximab; Lenalidomide

Study Results

Participant Flow

Recruitment Details	Recruitment Period: February 7, 2006 to February 21, 2011. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment Detail	There were 112 participants recruited for registration, 58 were screen failures prior to study inclusion

Arm/Group Title	Phase I: Lenalidomide + Rituximab	Phase II: Lenalidomide 20 mg + Rituximab
Arm/Group Description	Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks	Lenalidomide MTD Dose 20 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
Period Title: Phase I Dose Escalation Period
STARTED	14	0
Cohort 1: 10 mg	3	0
Cohort 2: 15 mg	3	0
Cohort 3: 20 mg	6	0
Cohort 4: 25 mg	2	0
COMPLETED	14	0
NOT COMPLETED	0	0
Period Title: Phase I Dose Escalation Period
STARTED	6	38
COMPLETED	6	38
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phase 1: Lenalidomide + Rituximab	Phase II: Lenalidomide 20 mg + Rituximab	Total
Arm/Group Description	Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks	Lenalidomide MTD Dose 20 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks	Total of all reporting groups
Overall Participants	14	38	52
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	72	64	66
Sex: Female, Male (Count of Participants)
Female	2 14.3%	3 7.9%	5 9.6%
Male	12 85.7%	35 92.1%	47 90.4%
Region of Enrollment (participants) [Number]
United States	14 100%	38 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Lenalidomide in Combination With Rituximab
Description	MTD is defined as the highest dose level in which 1 or fewer participants experienced a dose limiting toxicity (DLT) in 6 participants treated. DLT is any grade III or IV toxicity during the first 28 days (first cycle) of therapy.
Time Frame	28 days of cycle 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I: Lenalidomide + Rituximab
Arm/Group Description	Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
Measure Participants	14
Number [mg]	20

2. Secondary Outcome

Title	Response of Participants Treated at Lenalidomide 20 mg
Description	Response definitions for measurable disease from the International Workshop Standardized Response Criteria for non-Hodgkin's Lymphoma: Complete Response (CR): Disappearance of all clinical evidence of active tumor for a minimum of four weeks. Partial Response (PR): =/>50% decrease in sum of products of all measured lesions persisting for >four weeks. No lesion may increase in size & no new lesion may appear. Minor Response (MR): >25% but less than 50% response. Stable Disease: Steady state or response less than minor & no progression for at least 8 weeks. There may be no appearance of significant new lesions. Progressive Disease: Unequivocal increase in size of any measurable lesion or appearance of significant new.
Time Frame	56 days, assessed after 2 cycles

Outcome Measure Data

Analysis Population Description

Total analyzed includes Phase 2 participants (38) which includes six participants (6) that continued from Phase 1 who were treated with 20 mg Lenalidomide.

Arm/Group Title	Lenalidomide 20 mg + Rituximab
Arm/Group Description	Lenalidomide MTD Dose 20 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
Measure Participants	44
Complete Response	16 114.3%
Partial Response	9 64.3%
Stable Disease	10 71.4%
Progressive Disease	9 64.3%

3. Secondary Outcome

Title	Objective Response Rate of Participants Treated With Lenalidomide 20 mg: Overall Response as % of Participants With Complete or Partial Response
Description	Objective response rate defined as percentage of participants with complete or partial response after 2 cycles of therapy maintained for one month. Objective response monitored using Simon's optimal 2-stage design.
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

Total analyzed includes Phase 2 participants (38) which includes six participants (6) that continued from Phase 1 who were treated with 20 mg Lenalidomide.

Arm/Group Title	Lenalidomide + Rituximab
Arm/Group Description	Lenalidomide Starting Dose 10 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
Measure Participants	44
Number [percentage of participants]	57 407.1%

Adverse Events

Time Frame	From date of randomization until the date of death from any cause or study completion, whichever came first, assessed up to 10 years
Adverse Event Reporting Description	Phase 1 included a total 14 participants in the MTD determination while Phase 2 included 38 additional participants, reflected in the Adverse Reporting are 6 participants from Phase I dosed at 20 mg MTD to total 44 participants in that portion of the study.
Arm/Group Title	Phase I: Lenalidomide + Rituximab		Phase II: Lenalidomide
Arm/Group Description	Lenalidomide Starting Dose 10 mg, 15 mg, 20 mg or 25 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks		Lenalidomide MTD Dose 20 mg oral daily on Days 1-21 + Rituximab 375 mg/m^2 intravenous weekly for 4 weeks
All Cause Mortality
	Phase I: Lenalidomide + Rituximab		Phase II: Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		0/44 (0%)
Serious Adverse Events
	Phase I: Lenalidomide + Rituximab		Phase II: Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/14 (64.3%)		24/44 (54.5%)
Blood and lymphatic system disorders
Neutropenia	5/14 (35.7%)	5	13/44 (29.5%)	13
Lymphopenia	0/14 (0%)	0	4/44 (9.1%)	4
Cardiac disorders
Chest Pain	0/14 (0%)	0	2/44 (4.5%)	2
General disorders
Abdominal Pain	0/14 (0%)	0	1/44 (2.3%)	1
Death	1/14 (7.1%)	1	0/44 (0%)	0
Infections and infestations
Non-neutropenic infections	1/14 (7.1%)	1	0/44 (0%)	0
Injury, poisoning and procedural complications
Post Radiation Treatment Complication	0/14 (0%)	0	1/44 (2.3%)	1
Investigations
Leucopenia/leukocytopenia	1/14 (7.1%)	1	3/44 (6.8%)	3
Metabolism and nutrition disorders
Hyperuricemia	1/14 (7.1%)	1	1/44 (2.3%)	1
Hypercalcaemia	1/14 (7.1%)	1	2/44 (4.5%)	2
Hypophosphatemia	0/14 (0%)	0	1/44 (2.3%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	0/14 (0%)	0	2/44 (4.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Progression	0/14 (0%)	0	1/44 (2.3%)	1
Nervous system disorders
Cerebral edema	0/14 (0%)	0	1/44 (2.3%)	1
Snyocope	0/14 (0%)	0	1/44 (2.3%)	1
Psychiatric disorders
Altered mental Status	0/14 (0%)	0	1/44 (2.3%)	1
Renal and urinary disorders
Acute Renal Insufficiency	0/14 (0%)	0	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/14 (0%)	0	2/44 (4.5%)	2
Pneumonia	0/14 (0%)	0	2/44 (4.5%)	2
Dyspnea	0/14 (0%)	0	1/44 (2.3%)	1
Skin and subcutaneous tissue disorders
Cellulitis	0/14 (0%)	0	1/44 (2.3%)	1
Vascular disorders
Thrombosis or thromboembolism	0/14 (0%)	0	1/44 (2.3%)	1
Deep Vein Thrombosis	0/14 (0%)	0	2/44 (4.5%)	3
Thrombocytopenia	1/14 (7.1%)	1	4/44 (9.1%)	5
Other (Not Including Serious) Adverse Events
	Phase I: Lenalidomide + Rituximab		Phase II: Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		44/44 (100%)
Blood and lymphatic system disorders
Anaemia	14/14 (100%)	14	38/44 (86.4%)	38
Neutropenia	14/14 (100%)	14	44/44 (100%)	71
Febrile neutropenia	3/14 (21.4%)	3	10/44 (22.7%)	10
Thrombocytopenia	14/14 (100%)	14	42/44 (95.5%)	42
Leucopenia	13/14 (92.9%)	13	44/44 (100%)	53
Lymphopenia	14/14 (100%)	14	44/44 (100%)	64
Eye disorders
Blurred vision	0/14 (0%)	0	15/44 (34.1%)	15
Red eyes	0/14 (0%)	0	16/44 (36.4%)	16
Gastrointestinal disorders
Constipation	0/14 (0%)	0	30/44 (68.2%)	30
Nausea	0/14 (0%)	0	20/44 (45.5%)	20
Vomiting	0/14 (0%)	0	15/44 (34.1%)	15
Oral cavity pain	0/14 (0%)	0	15/44 (34.1%)	15
Abdominal pain	0/14 (0%)	0	11/44 (25%)	11
Diarrhoea	0/14 (0%)	0	29/44 (65.9%)	29
General disorders
Fatigue	14/14 (100%)	14	38/44 (86.4%)	58
Non-neutropenic infections	14/14 (100%)	14	28/44 (63.6%)	28
Facial oedema	0/14 (0%)	0	4/44 (9.1%)	4
Oedema limb	0/14 (0%)	0	20/44 (45.5%)	20
Hepatobiliary disorders
Thrombosis or thromboembolism	0/14 (0%)	0	3/44 (6.8%)	3
Investigations
Increased liver function	11/14 (78.6%)	11	18/44 (40.9%)	18
Metabolism and nutrition disorders
Hyperglycaemia	14/14 (100%)	14	41/44 (93.2%)	41
Hyperuricaemia	7/14 (50%)	7	14/44 (31.8%)	14
Hypercalcaemia	2/14 (14.3%)	2	3/44 (6.8%)	3
Hypophosphataemia	0/14 (0%)	0	8/44 (18.2%)	8
Hyperkalaemia	0/14 (0%)	0	3/44 (6.8%)	3
Hypoalbuminaemia	0/14 (0%)	0	14/44 (31.8%)	14
Hypomagnesaemia	0/14 (0%)	0	15/44 (34.1%)	15
Raised blood urea nitrogen (BUN)	0/14 (0%)	0	10/44 (22.7%)	10
Raised Beta-2-Microglobulin (B2M)	0/14 (0%)	0	13/44 (29.5%)	13
Raised Lactate dehydrogenase (LDH or LD)	0/14 (0%)	0	13/44 (29.5%)	13
Musculoskeletal and connective tissue disorders
Limb pain	5/14 (35.7%)	5	7/44 (15.9%)	7
Myalgia	6/14 (42.9%)	6	30/44 (68.2%)	30
Nervous system disorders
Ataxia	1/14 (7.1%)	1	2/44 (4.5%)	2
Syncope	1/14 (7.1%)	1	0/44 (0%)	0
Neuropathy	0/14 (0%)	0	33/44 (75%)	33
Memory impairment	0/14 (0%)	0	13/44 (29.5%)	13
Dizziness	0/14 (0%)	0	18/44 (40.9%)	18
Psychiatric disorders
Mood alteration	0/14 (0%)	0	12/44 (27.3%)	12
Respiratory, thoracic and mediastinal disorders
Cough	10/14 (71.4%)	10	19/44 (43.2%)	19
Dyspnoea	0/14 (0%)	0	23/44 (52.3%)	23
Pleural effusion	0/14 (0%)	0	6/44 (13.6%)	6
Rhinorrhoea	0/14 (0%)	0	19/44 (43.2%)	19
Skin and subcutaneous tissue disorders
Pruritus	13/14 (92.9%)	13	22/44 (50%)	22
Rash	0/14 (0%)	0	29/44 (65.9%)	29

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.