Combination Chemotherapy and Alemtuzumab in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

National Cancer Institute (NCI)

Status and phase: Terminated; Phase 2

Conditions: Recurrent Adult Acute Lymphoblastic Leukemia

Treatments: Drug: leucovorin calcium; Drug: mercaptopurine; Biological: alemtuzumab; Drug: asparaginase; Drug: dexamethasone; Drug: methotrexate; Drug: vincristine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00262925

E1904 (Other Identifier)

NCI-2009-00518

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Treatment (chemotherapy, enzyme inhibitor therapy)

Experimental group

Description:

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.

Treatment:

Drug: vincristine

Drug: methotrexate

Drug: dexamethasone

Drug: asparaginase

Drug: mercaptopurine

Biological: alemtuzumab

Drug: leucovorin calcium