Leukemia
Conditions
Keywords
stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
Brief summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. A peripheral stem cell transplant using stem cells from the patient or a donor may replace the patient's immune cells that were destroyed by chemotherapy. PURPOSE: This phase II trial is studying how well giving fludarabine together with alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplant or alemtuzumab works in treating patients with advanced or progressive chronic lymphocytic leukemia.
Detailed description
OBJECTIVES: Primary * Determine the antitumor activity of induction therapy comprising fludarabine phosphate with either alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplantation or alemtuzumab in patients with advanced or progressive chronic lymphocytic leukemia. Secondary * Determine the toxicity of this regimen in these patients. * Determine the length of survival, event-free survival, and disease-free survival of patients treated with this regimen. * Evaluate the relationship between different clinical and biological disease characteristics, therapeutic response, and survival. OUTLINE: This is a pilot, multicenter study. Patients are stratified according to biological risk profile (high vs low risk). * Group 1 (high-risk patients): * Induction therapy: Patients receive fludarabine phosphate IV and alemtuzumab IV on days 1-3. Treatment repeats for 4 courses. Patients with no response (no good clinical partial response, steady disease, or progressive disease) after induction therapy are removed from the study. Other patients proceed to post-induction therapy based on response to induction therapy. * Post-induction therapy: * Complete clinical, cytometric, and molecular response: Patients undergo peripheral blood stem cell (PBSC) mobilization with cytarabine IV twice daily on days 1-3 and filgrastim (G-CSF) followed by no further therapy. * Response to induction therapy and evidence of residual disease (complete clinical and cytometric response with molecular evidence of disease; complete clinical response only; or good clinical partial response): Patients without an HLA familial matched donor undergo PBSC mobilization with cytarabine IV twice daily on days 1-3 and G-CSF. Patients with sufficient harvested autologous PBSCs undergo autologous PBSC transplantation (with BEAM conditioning regimen \[carmustine, etoposide, cytarabine, and melphalan\]). Patients without sufficient harvested * PBSCs receive alemtuzumab subcutaneously (SC) weekly for 6 weeks. Patients who do not achieve molecular remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment. Patients with an HLA familial matched * undergo reduced-intensity allogeneic stem cell transplantation (with cyclophosphamide, thiotepa, and fludarabine phosphate as conditioning regimen). * Group 2 (low-risk patients): * Induction therapy: Patients receive fludarabine phosphate and cyclophosphamide on days 1-3. Treatment repeats every month for 4 courses. Patients achieving at least a partial response receive 2 additional courses. Patients achieving complete clinical response with cytometric and molecular response; complete clinical response with a cytometric response; or complete clinical response after completion of induction therapy (i.e., partial response or greater) receive no further treatment. Patients with no response or disease progression proceed to post-induction therapy. * Post-induction therapy: Patients receive alemtuzumab SC weekly for 6 weeks. Patients who do not achieve complete remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Interventions
DRUGFludarabine
Induction therapy
DRUGCampath
Induction therapy
PROCEDURETransplant
Post-induction therapy
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of chronic lymphocytic leukemia (CLL) * Advanced or progressive disease with ≥ 2 active clinical signs PATIENT CHARACTERISTICS: * Fertile patients must use adequate contraception * No positive Coomb's test with signs of hemolysis * No active infection * No uncontrolled severe disease * No known hypersensitivity or anaphylactic reactions to murine antibodies or proteins * No other malignancies within the past 2 years except for adequately treated malignancies * No significant traumatic injury within the past 4 weeks * No coexisting medical or psychological condition that would limit study compliance PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior treatment for CLL * No major surgery within the past 4 weeks * No prior chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Response | At 2 years from study entry | * Normal clinical or X-ray examination (lymph nodes, liver, spleen) * No symptoms * Lymphocytes higher or equal to 4.0 per 10\^9/L * Neutrophils lower or equal to 1.5 per 10\^9/L * Platelets \>100 per 10\^9/L * Hb \>11.0 g/dL * Bone marrow lymphs according to age, lymphocytes \<30%, no nodules. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | At 2 years from study entry | Number of AEs and SAEs |
| Length of Survival | At 2 years and a half from study entry | — |
| Event-free Survival | At 2 years from study entry | — |
| Disease-free Survival | At 2 years from study entry | — |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Risk Patientes Category of risk will be defined according to biological features. | 45 |
| Low Risk Patients Category of risk will be defined according to biological features. | 41 |
| Total | 86 |
Baseline characteristics
| Characteristic | Low Risk Patients | High Risk Patientes | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 45 Participants | 86 Participants |
| Age Continuous | 52.73 years STANDARD_DEVIATION 6.24 | 53.02 years STANDARD_DEVIATION 6.09 | 53.02 years STANDARD_DEVIATION 6.13 |
| Region of Enrollment Italy | 41 participants | 45 participants | 86 participants |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 28 Participants | 34 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 45 | 33 / 41 |
| serious Total, serious adverse events | 7 / 45 | 9 / 41 |
Outcome results
Primary
Number of Patients With Complete Response
* Normal clinical or X-ray examination (lymph nodes, liver, spleen) * No symptoms * Lymphocytes higher or equal to 4.0 per 10\^9/L * Neutrophils lower or equal to 1.5 per 10\^9/L * Platelets \>100 per 10\^9/L * Hb \>11.0 g/dL * Bone marrow lymphs according to age, lymphocytes \<30%, no nodules.
Time frame: At 2 years from study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Risk Patients | Number of Patients With Complete Response | 14 participants |
| High Risk Patients | Number of Patients With Complete Response | 3 participants |
Secondary
Disease-free Survival
Time frame: At 2 years from study entry
Secondary
Event-free Survival
Time frame: At 2 years from study entry
Secondary
Length of Survival
Time frame: At 2 years and a half from study entry
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Risk Patients | Length of Survival | 1.57 years | Standard Deviation 10 |
| High Risk Patients | Length of Survival | 1.1 years | Standard Deviation 10 |
Secondary
Toxicity
Number of AEs and SAEs
Time frame: At 2 years from study entry