Leukemia
Conditions
Keywords
refractory chronic lymphocytic leukemia
Brief summary
RATIONALE: Biological therapies such as lenalidomide use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining lenalidomide with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying the how well giving lenalidomide with or without rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia.
Detailed description
OBJECTIVES: Primary * Determine the best cytostatic response rate (including complete response, partial response, or stable disease) in patients with relapsed or refractory chronic lymphocytic leukemia treated with lenalidomide (CC-5013). Secondary * Determine the cytostatic response rate in patients who progress on CC-5013 and are then treated with CC-5013 and rituximab. * Determine the safety of these regimens in these patients. * Determine time to progression in patients treated with these regimens. OUTLINE: This is an open-label, non-randomized, pilot study. Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) receive 2 additional courses beyond CR. Patients with disease progression receive oral CC-5013 once daily on days 1-21 and rituximab IV on days 1, 8, and 15 during the first treatment course and on days 1 and 15 of all subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of further disease progression. Patients who achieve CR receive 2 additional courses beyond CR. Patients are followed at 1 month and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 1.5 years.
Interventions
DRUGlenalidomide
Oral
BIOLOGICALrituximab
IV
Sponsors
Celgene
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of chronic lymphocytic leukemia (CLL) by flow cytometry * Relapsed or refractory disease * Measurable disease, defined by 1 of the following criteria: * Absolute lymphocyte count ≥ 5,000/mm\^3 * Measurable lymphadenopathy or organomegaly * Received ≥ 1 prior therapy for CLL PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * See Disease Characteristics * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 30,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 mg/dL * AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present) Renal * Creatinine ≤ 1.5 mg/dL Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective double-method (including barrier) contraception during and for 3 months after study participation * No known hypersensitivity to thalidomide * No erythema nodosum characterized by a desquamating rash after prior thalidomide or similar drug administration * No known anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins * No serious medical condition or laboratory abnormality that would preclude study participation * No psychiatric illness that would preclude giving informed consent PRIOR CONCURRENT THERAPY: Biologic therapy * No prior lenalidomide (CC-5013) * No concurrent thalidomide Chemotherapy * Not specified Endocrine therapy * Not specified Radiotherapy * No concurrent radiotherapy Surgery * Not specified Other * At least 4 weeks since prior therapy for CLL * At least 28 days since prior experimental drug or therapy * No other concurrent anticancer therapies * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months | at 6 Months | Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count \>1500/μL; platelet count \>100,000/μL; untransfused hemoglobin concentration \>11.0g/dL; lymphocyte count \<4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab | 5 years | Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count \>1500/μL; platelet count \>100,000/μL; untransfused hemoglobin concentration \>11.0g/dL; lymphocyte count \<4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD. |
| Number of Participants With Adverse Events on Single Agent CC-5013 | 1 year | Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail. |
| Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab. | Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0 |
| Time to Progression for Single Agent CC-5013 | 5 years | Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. |
| Time to Progression for the Combination Therapy of CC-5013+Rituximab | Every month up to 6 months and every 3 months thereafter up to 5 years | Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Lenalidomide Patients receive oral lenalidomide (CC-5013) once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity
rituximab: IV
lenalidomide: Oral | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 21 |
| Overall Study | Disease Progression | 4 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Oral Lenalidomide |
|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 44 / 45 |
| serious Total, serious adverse events | 29 / 45 |
Outcome results
Primary
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months
Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count \>1500/μL; platelet count \>100,000/μL; untransfused hemoglobin concentration \>11.0g/dL; lymphocyte count \<4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.
Time frame: at 6 Months
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Lenalidomide | Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Single Agent CC-5013 at 6 Months | 68.9 percentage of participants |
Secondary
Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab
Number of Participants with Adverse Events on Combination Therapy of CC-5013+Rituximab, Graded According to NCI CTCAE Version 3.0
Time frame: Up to 30 days from last date of institution of combination therapy of CC-5013+Rituximab.
Population: All treated with combination therapy of CC-5013+Rituximab and eligible patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Lenalidomide | Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Grade 1 | 1 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Grade 2 | 0 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Grade 3 | 3 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Combination Therapy of CC-5013+Rituximab | Grade 4 | 3 Participants |
Secondary
Number of Participants With Adverse Events on Single Agent CC-5013
Number of Participants with Adverse Events on Single Agent CC-5013, Graded According to NCI CTCAE Version 3.0 Please refer to the adverse event reporting for more detail.
Time frame: 1 year
Population: All treated and eligible patients
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Lenalidomide | Number of Participants With Adverse Events on Single Agent CC-5013 | Grade 2 | 3 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Single Agent CC-5013 | Grade 3 | 7 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Single Agent CC-5013 | Grade 1 | 0 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Single Agent CC-5013 | Grade 4 | 33 Participants |
| Oral Lenalidomide | Number of Participants With Adverse Events on Single Agent CC-5013 | Grade 5 | 2 Participants |
Secondary
Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab
Percentage of patients achieving CR, PR or maintaining SD using the 1996 NCI-WF Criteria. CR: absence of lymph nodes and constitutional symptoms; no hepatomegaly or splenomegaly by physical examination; neutrophil count \>1500/μL; platelet count \>100,000/μL; untransfused hemoglobin concentration \>11.0g/dL; lymphocyte count \<4000/μL; bone marrow sample must be at least normocellular for age; with less than 30% of nucleated cells being lymphocytes and no lymphoid nodules. PR: ≥50% decrease in lymphocyte count from baseline; ≥50% reduction in lymph nodes from baseline; ≥50% reduction in the size of the liver/spleen from baseline; neutrophil count ≥1500/μL or ≥50% improvement from baseline; platelet count ≥100,000/μL or ≥50% improvement from baseline; untransfused hemoglobin concentration ≥11.0g/dL or ≥50% improvement from baseline. Patients who have not exhibited as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow, are considered to have SD.
Time frame: 5 years
Population: All treated with combination therapy of CC-5013+Rituximab and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Lenalidomide | Percentage of Patients Achieving a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) on Combination Therapy of CC-5013+Rituximab | 100 percentage of participants |
Secondary
Time to Progression for Single Agent CC-5013
Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.
Time frame: 5 years
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Lenalidomide | Time to Progression for Single Agent CC-5013 | 23.0 months |
Secondary
Time to Progression for the Combination Therapy of CC-5013+Rituximab
Progressive disease is defined as reappearance of malignant CLL clone on flow cytometry or by PCR analysis in blood or bone marrow using the 1996 NCI-WF Criteria.
Time frame: Every month up to 6 months and every 3 months thereafter up to 5 years
Population: All treated with combination therapy of CC-5013+Rituximab and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oral Lenalidomide | Time to Progression for the Combination Therapy of CC-5013+Rituximab | 18.7 months |