Clinical trial NCT00262925
Conditions: Recurrent Adult Acute Lymphoblastic Leukemia
Keywords: MOAD Methotrexate Vincristine L-asparaginase Dexamethasone Subcutaneous Campath
Sponsor: National Cancer Institute (NCI)
Start date: 2006-06-01; Completion date: 2013-02-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: INDUCTION THERAPY: Patients receive methotrexate IV; vincristine IV and asparaginase IM ; oral dexamethasone ; and alemtuzumab SC.

CONSOLIDATION THERAPY: Patients receive methotrexate IV and asparaginase IM.

CYTOREDUCTION THERAPY: Patients receive vincristine IV and methotrexate IV; leucovorin calcium IV; and oral dexamethasone.

MAINTENANCE THERAPY: Patients receive oral mercaptopurine; oral methotrexate; vincristine IV; and oral dexamethasone.
Interventions: intervention 1: alemtuzumab intervention 2: asparaginase intervention 3: methotrexate intervention 4: dexamethasone intervention 5: leucovorin calcium intervention 6: mercaptopurine intervention 7: vincristine
Intervention descriptions: intervention 1: Given subcutaneously intervention 2: Given IM intervention 3: Given IV or orally intervention 4: Given orally intervention 5: Given IV intervention 6: Given orally intervention 7: Given IV

Protocol documents: