Recurrent Adult Acute Lymphoblastic Leukemia
Conditions
Keywords
MOAD, Methotrexate, Vincristine, L-asparaginase, Dexamethasone, Subcutaneous Campath
Brief summary
This phase II trial is studying how well giving combination chemotherapy together with alemtuzumab works in treating patients with relapsed or refractory acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. 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. Giving combination chemotherapy together with alemtuzumab may kill more cancer cells.
Detailed description
OBJECTIVES: I. Determine the complete response rate in patients with relapsed or refractory acute lymphoblastic leukemia treated with methotrexate, vincristine, asparaginase, and dexamethasone (MOAB) in combination with alemtuzumab. II. Determine disease-free and/or overall survival of patients treated with this regimen. III. Determine the toxic effects of this regimen in these patients. IV. Correlate the density of cluster of differentiation 52 (CD52) molecules on the surface of leukemic lymphoblasts with response in patients treated with this regimen. V. Correlate the presence of minimal residual disease at the time of maximal response to this regimen with overall outcome in these patients. OUTLINE: This is a multicenter study. The study had two steps. Step 1: 5 mg dose of Campath (alemtuzumab); Step 2: 10 mg dose of Campath. INDUCTION THERAPY: Patients receive methotrexate intravenously (IV) on day 1; vincristine IV and asparaginase intramuscularly (IM) on day 2; oral dexamethasone on days 1-10; and alemtuzumab subcutaneously (SC) on days 1, 4, and 7. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) proceed to consolidation therapy. CONSOLIDATION THERAPY: Patients receive methotrexate IV on day 1 and asparaginase IM on day 2. Treatment repeats every 10 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to cytoreduction therapy. CYTOREDUCTION THERAPY: Patients receive vincristine IV and methotrexate IV over 6 hours on day 1; leucovorin calcium IV continuously over 24 hours on days 1 and 2 and then orally 4 times a day on day 3; and oral dexamethasone on days 2-6. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in CR proceed to maintenance therapy. MAINTENANCE THERAPY: Patients receive oral mercaptopurine on days 1-30; oral methotrexate on days 1, 8, 15, and 22; vincristine IV on day 1; and oral dexamethasone on days 1-5. Treatment repeats every 30 days for 36 courses in the absence of disease progression or unacceptable toxicity. Patients are assessed every 3 months if patient is \< 2 years from study entry and every 6 months if patient is 2-5 years from study entry. PROJECTED ACCRUAL: Allowing for two dose levels, a maximum of 48 patients may be accrued approximately in 30 months.
Interventions
BIOLOGICALalemtuzumab
Given subcutaneously
DRUGasparaginase
Given IM
DRUGmethotrexate
Given IV or orally
DRUGdexamethasone
Given orally
DRUGleucovorin calcium
Given IV
DRUGmercaptopurine
Given orally
DRUGvincristine
Given IV
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Refractory or relapsed acute lymphoblastic leukemia * Must be in first relapse or have failed to achieve complete remission with 1 prior regimen * Prior central nervous system (CNS) leukemia allowed provided cerebrospinal fluid is normal * ECOG Performance status of 0-3 * Bilirubin normal * Creatinine normal * Human immunodeficiency virus (HIV) negative * Negative pregnancy test * Fertile patients must use effective contraception
Exclusion criteria
* Hepatitis B positivity * Bacterial or fungal infection * Infection requiring treatment with antibiotics * Active cytomegalovirus infection by molecular detection methods * Known hypersensitivity to alemtuzumab or its components * Pregnant or nursing * Other malignancy within the past 5 years except adequately treated basal cell skin cancer or cervical carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | assessed before the first consolidation cycle and first cytoreduction cycle, before the first and after the last maintenance cycle; after discontinuing treatment, assessed every 3 months if < 2 years and every 6 months if 2-5 years from study entry | Complete response requires that all of the following be present for at least four weeks. 1\. Peripheral Blood Counts: Neutrophil count \>= 1.0 x 109/L, Platelet count \>= 100 x 109/L, Reduced hemoglobin concentration or hematocrit has no bearing on remission status, Leukemic blasts must not be present in the peripheral blood. 2 .Bone Marrow Aspirate and Biopsy: Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines, \<= 5% blasts. 3\. Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry | Time from registration to death from any cause. Patients alive were censored at follow up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy, Enzyme Inhibitor Therapy) INDUCTION THERAPY: Patients receive methotrexate IV; vincristine IV and asparaginase IM; oral dexamethasone; and alemtuzumab SC on days 1, 4, and 7.
CONSOLIDATION THERAPY: Patients receive methotrexate IV and asparaginase IM.
CYTOREDUCTION THERAPY: Patients receive vincristine IV and oral methotrexate IV; leucovorin calcium IV; and oral dexamethasone.
MAINTENANCE THERAPY: Patients receive oral mercaptopurine; oral methotrexate; vincristine IV; and oral dexamethasone. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | alternative therapy | 1 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy, Enzyme Inhibitor Therapy) |
|---|---|
| Age, Customized | 35 years |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 5 / 5 |
| serious Total, serious adverse events | 7 / 7 | 5 / 5 |
Outcome results
Primary
Complete Response Rate
Complete response requires that all of the following be present for at least four weeks. 1\. Peripheral Blood Counts: Neutrophil count \>= 1.0 x 109/L, Platelet count \>= 100 x 109/L, Reduced hemoglobin concentration or hematocrit has no bearing on remission status, Leukemic blasts must not be present in the peripheral blood. 2 .Bone Marrow Aspirate and Biopsy: Cellularity of bone marrow biopsy must be \> 20% with maturation of all cell lines, \<= 5% blasts. 3\. Extramedullary leukemia, such as CNS or soft tissue involvement, must not be present.
Time frame: assessed before the first consolidation cycle and first cytoreduction cycle, before the first and after the last maintenance cycle; after discontinuing treatment, assessed every 3 months if < 2 years and every 6 months if 2-5 years from study entry
Population: all enrolled patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, Enzyme Inhibitor Therapy) | Complete Response Rate | 33 percentage of participants |
Secondary
Overall Survival
Time from registration to death from any cause. Patients alive were censored at follow up.
Time frame: assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, Enzyme Inhibitor Therapy) | Overall Survival | 5.2 months |