Clinical trial NCT00061945: Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Undifferentiated Leukemia
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
L1 Adult Acute Lymphoblastic Leukemia
L1 Childhood Acute Lymphoblastic Leukemia
L2 Adult Acute Lymphoblastic Leukemia
L2 Childhood Acute Lymphoblastic Leukemia
Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-06-06
Enrollment: 302
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)
timeFrame: 6 weeks
measure: Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II)
timeFrame: 8 months
Secondary outcomes:
measure: Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II)
timeFrame: 9 years 4 months
measure: Disease-free Survival, for Only Complete Response Patients
timeFrame: 9 years 4 months
measure: Overall Survival
timeFrame: 9 years 4 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Cancer and Leukemia Group B
state: Illinois
Study officials:
affiliation: Cancer and Leukemia Group B
name: Wendy Stock
role: PRINCIPAL_INVESTIGATOR
References: