Trials / Completed

CompletedNCT00061945

Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

Status: Completed
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 302 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 15 Years
Healthy volunteers: Not accepted

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.

Conditions

Interventions

Type	Name	Description
DRUG	allopurinol	Given PO
DRUG	cyclophosphamide	Given IV
DRUG	daunorubicin hydrochloride	Given IV
DRUG	vincristine sulfate	Given IV
DRUG	dexamethasone	Given PO and as eye drops
DRUG	asparaginase	Given SC
BIOLOGICAL	filgrastim	Given SC
DRUG	imatinib mesylate	Given PO
DRUG	methotrexate	Given IT, IV, and PO
DRUG	cytarabine	Given IV
DRUG	trimethoprim-sulfamethoxazole	Given PO
DRUG	mercaptopurine	Given PO
DRUG	leucovorin calcium	Given IV and PO
BIOLOGICAL	alemtuzumab	Given SC
DRUG	acyclovir	Given PO
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

Start date: 2003-06-01
Primary completion: 2007-12-01
Completion: 2012-10-01
First posted: 2003-06-06
Last updated: 2022-05-03
Results posted: 2014-04-16

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00061945. Inclusion in this directory is not an endorsement.