Trial Information

A Feasibility Pilot and Phase 2 Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)

PRIMARY OBJECTIVES:

I. Determine the feasibility of epratuzumab administered alone and in combination with
re-induction combination chemotherapy in pediatric patients with relapsed CD22-positive
acute lymphoblastic leukemia.

II. Determine the toxic effects of this regimen in these patients. III. Determine the
antitumor activity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of epratuzumab in these patients. II. Determine the
biologic activity of epratuzumab using measurements of minimal residual disease in these
patients.

III. Determine the human anti-human antibody (HAHA) response in patients treated with this
regimen.

OUTLINE: This is a multicenter study comprising a feasibility part A (closed to accrual as
of 10/30/06) followed by a pilot part B study. Patients enrolled in part B are stratified
according to relapse (first early marrow relapse occurring < 36 months from initial
diagnosis vs first late marrow relapse occurring ≥ 36 months from initial diagnosis vs in
second or subsequent relapse).

PART A (CLOSED TO ACCRUAL 10/30/06):

REDUCTION THERAPY: Patients receive epratuzumab IV over 1 hour on days -14, -10, -6, and -2
and cytarabine intrathecally (IT) on day -14*.

NOTE: *Patients who receive IT chemotherapy within 7 days of study entry as prior
maintenance chemotherapy (e.g., before the diagnosis of relapse) will not receive this first
dose of IT cytarabine.

RE-INDUCTION THERAPY (BLOCK 1): Patients receive vincristine IV on days 1, 8, 15, and 22;
oral prednisone two or three times daily on days 1-29; pegaspargase intramuscularly (IM) on
days 2, 9, 16, and 23; dexrazoxane IV followed by doxorubicin IV over 15 minutes on day 1;
methotrexate IT on days 15 and 29 for CNS-negative disease; and epratuzumab IV over 1 hour
on days 8, 15, 22, and 29. Patients with CNS-positive disease also receive triple IT therapy
(ITT) consisting of methotrexate, cytarabine, hydrocortisone on days -10, -6, 1 and 15.

RE-INDUCTION THERAPY (BLOCK 2): Beginning at least 7 days after the last dose of IT
chemotherapy, patients receive etoposide IV over 2 hours and cyclophosphamide IV over 30
minutes on days 1-5. Patients also receive high-dose methotrexate IV continuously over 24
hours on day 22. Beginning 42 hours after the start of the methotrexate infusion (day 24),
patients receive leucovorin calcium IV every 6 hours for a minimum of 3 doses. Patients with
CNS-negative disease also receive methotrexate IT on days 1 and 22. Patients with
CNS-positive disease will receive triple IT as in re-induction therapy (block 1) on days 1
and 22. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day
6 and continuing until blood counts recover.

RE-INDUCTION THERAPY (PART 3): Beginning at least 7 days after the last dose of IT
chemotherapy, patients receive cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9
and asparaginase IM on days 2 and 9. Patients receive G-CSF SC once daily beginning on day
10 and continuing until blood counts recover.

PART B:

RE-INDUCTION THERAPY (BLOCK 1): Patients receive vincristine, prednisone, pegaspargase,
doxorubicin, cytarabine, methotrexate, and epratuzumab as in phase I re-induction therapy
(block 1). Patients with CNS-negative disease receive methotrexate IT on days 1 and 22.
Patients with CNS-positive disease receive triple IT therapy comprising methotrexate,
cytarabine, and hydrocortisone on days 8, 15, 22, and 29.

RE-INDUCTION THERAPY (BLOCKS 2 AND 3): Patients receive re-induction therapy blocks 2 and 3
as in the part A re-induction therapy (blocks 2 and 3) portion of the study.

Patients are followed annually.