Trial Information

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)

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).

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.