Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia
- Conditions
- Acute Undifferentiated LeukemiaB-cell Adult Acute Lymphoblastic LeukemiaB-cell Childhood Acute Lymphoblastic LeukemiaL1 Adult Acute Lymphoblastic LeukemiaL1 Childhood Acute Lymphoblastic LeukemiaL2 Adult Acute Lymphoblastic LeukemiaL2 Childhood Acute Lymphoblastic LeukemiaPhiladelphia Chromosome Negative Adult Precursor Acute Lymphoblastic LeukemiaPhiladelphia Chromosome Positive Adult Precursor Acute Lymphoblastic LeukemiaPhiladelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
- Interventions
- Biological: filgrastimDrug: trimethoprim-sulfamethoxazoleBiological: alemtuzumabOther: laboratory biomarker analysisOther: pharmacological study
- Registration Number
- NCT00061945
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. 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. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the feasibility and toxicity profiles of escalating doses of Campath-1H (alemtuzumab) given subcutaneously during post-remission intensification treatment of adults with acute lymphoblastic leukemia (ALL).
II. To determine the disease-free survival (DFS) and overall survival (OS) when Campath-1H is used during post-remission intensification treatment of adults with ALL.
III. To determine whether antibody treatment with Campath-1H can further reduce minimal residual disease states in adult ALL.
IV. To obtain preliminary descriptive data on serum levels of Campath-1H during course IV, module D using limited pharmacokinetic sampling during the phase I and II components of the study.
V. To obtain feasibility data on the addition of imatinib to Cancer and Leukemia Group B (CALGB) induction and postremission combination chemotherapy for patients with Philadelphia chromosome positive (Ph+) ALL.
OUTLINE: This is a dose-escalation study of alemtuzumab.
COURSE 1 (module A): Patients receive allopurinol orally (PO) 4 times daily (QID) on days 1-14, cyclophosphamide\* intravenously (IV) over 15-30 minutes on day 1, daunorubicin hydrochloride IV on days 1-3, vincristine sulfate IV on days 1, 8, 15, and 22, dexamethasone PO twice daily (BID) on days 1-7 and 15-21, asparaginase subcutaneously (SC) on days 5, 8, 11, 15, 18, and 22, and filgrastim SC on days 4-11. Patients who are Ph+ also receive imatinib mesylate PO on days 15-28.
\*Note: Patients who are = 60 years old do not receive cyclophosphamide.
COURSE 2 (module B): Patients receive methotrexate intrathecally (IT) on day 1, cytarabine IV over 3 hours on days 1-3, dexamethasone as eye drops QID on days 1-4, trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-29, and cyclophosphamide, asparaginase and filgrastim as in course 1. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28.
COURSE 3 (module C): Patients receive vincristine sulfate IV on days 1, 15, and 29, methotrexate IV over 3 hours and IT on days 1, 15, and 19, methotrexate PO every 6 hours on days 1-2, 15-16, and 29-30, mercaptopurine PO on days 1-35, leucovorin calcium IV on days 2, 16, and 30, leucovorin calcium PO every 6 hours on days 3-4, and trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-43. Patients who are Ph+ also receive imatinib mesylate PO on days 1-42.
COURSE 4 (module D): Patients receive alemtuzumab SC 3 times weekly for 4 weeks and begin acyclovir PO QID for 6 months (continuing through course 8).
* Phase I Cohort 1: 10 mg
* Phase I Cohort 2: 20 mg
* Phase I Cohort 3/Phase II MTD: 30 mg
COURSE 5 (module A): Patients repeat course 1, minus allopurinol.
COURSE 6 (module B): Patients repeat course 2.
COURSE 7 (module C): Patients repeat course 3.
COURSE 8: Patients receive mercaptopurine PO, vincristine sulfate IV on day 1, dexamethasone PO on days 1-5, methotrexate PO on days 1, 8, 15, and 22, and trimethoprim-sulfamethoxazole PO BID 3 days weekly. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 10 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 302
-
Unequivocal histologic diagnosis of precursor B or precursor T lymphoblastic leukemia (World Health Organization [WHO] classification), L1 or L2 ALL or acute undifferentiated leukemia (AUL) (French-American-British Cooperative group [FAB] Classification); Burkitt-type ALL (FAB L3, surface immunoglobulin [SIg]+) are excluded
-
No prior treatment for leukemia with three permissible exceptions:
- Emergency leukapheresis II. Emergency treatment for hyperleukocytosis with hydroxyurea III. Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
-
All patients must have a pre-treatment bone marrow or peripheral blood sample submitted for central immunophenotyping; only those patients who express CD52 >= 10% in the leukemia blast cell channel will be eligible to receive Campath-1H during module D, course IV
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (alemtuzumab and combination chemotherapy) alemtuzumab See detailed description. Treatment (alemtuzumab and combination chemotherapy) daunorubicin hydrochloride See detailed description. Treatment (alemtuzumab and combination chemotherapy) vincristine sulfate See detailed description. Treatment (alemtuzumab and combination chemotherapy) dexamethasone See detailed description. Treatment (alemtuzumab and combination chemotherapy) asparaginase See detailed description. Treatment (alemtuzumab and combination chemotherapy) filgrastim See detailed description. Treatment (alemtuzumab and combination chemotherapy) imatinib mesylate See detailed description. Treatment (alemtuzumab and combination chemotherapy) methotrexate See detailed description. Treatment (alemtuzumab and combination chemotherapy) cytarabine See detailed description. Treatment (alemtuzumab and combination chemotherapy) trimethoprim-sulfamethoxazole See detailed description. Treatment (alemtuzumab and combination chemotherapy) mercaptopurine See detailed description. Treatment (alemtuzumab and combination chemotherapy) acyclovir See detailed description. Treatment (alemtuzumab and combination chemotherapy) laboratory biomarker analysis See detailed description. Treatment (alemtuzumab and combination chemotherapy) pharmacological study See detailed description. Treatment (alemtuzumab and combination chemotherapy) leucovorin calcium See detailed description. Treatment (alemtuzumab and combination chemotherapy) allopurinol See detailed description. Treatment (alemtuzumab and combination chemotherapy) cyclophosphamide See detailed description.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I) 6 weeks The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.
Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II) 8 months The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.
- Secondary Outcome Measures
Name Time Method Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II) 9 years 4 months Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative.
Disease-free Survival, for Only Complete Response Patients 9 years 4 months Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented.
Overall Survival 9 years 4 months Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented.
Trial Locations
- Locations (1)
Cancer and Leukemia Group B
🇺🇸Chicago, Illinois, United States