A Feasibility Pilot and Phase 2 Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)
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.
I. Determine the pharmacokinetics of epratuzumab in these patients. II. Determine the
biologic activity of epratuzumab using measurements of minimal residual disease in these
III. Determine the human anti-human antibody (HAHA) response in patients treated with this
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.
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of an intensive chemoimmunotherapy approach for the treatment of relapsed CD-22 positive B-precursor acute lymphoblastic leukemia
Children's Oncology Group
United States: Food and Drug Administration
|Baylor College of Medicine||Houston, Texas 77030|
|Johns Hopkins University||Baltimore, Maryland 21205|
|Mayo Clinic||Rochester, Minnesota 55905|
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|University of Mississippi Medical Center||Jackson, Mississippi 39216-4505|
|Medical University of South Carolina||Charleston, South Carolina 29425-0721|
|Midwest Children's Cancer Center||Milwaukee, Wisconsin 53226|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Loma Linda University Medical Center||Loma Linda, California 92354|
|Newark Beth Israel Medical Center||Newark, New Jersey 07112|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Eastern Maine Medical Center||Bangor, Maine 04401|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Children's National Medical Center||Washington, District of Columbia 20010-2970|
|Children's Hospital Central California||Madera, California 93638-8762|
|Primary Children's Medical Center||Salt Lake City, Utah 84113-1100|
|University of New Mexico Cancer Center||Albuquerque, New Mexico 87131-5636|
|Nationwide Children's Hospital||Columbus, Ohio 43205-2696|
|University of Alabama at Birmingham||Birmingham, Alabama 35294-3300|
|University of Rochester||Rochester, New York 14642|
|Wayne State University||Detroit, Michigan 48202|
|Indiana University Medical Center||Indianapolis, Indiana 46202|
|University of Kentucky||Lexington, Kentucky 40536-0098|
|Oregon Health and Science University||Portland, Oregon 97201|
|Tulane University Health Sciences Center||New Orleans, Louisiana 70112|
|David Geffen School of Medicine at UCLA||Los Angeles, California 90095|
|M D Anderson Cancer Center||Houston, Texas 77030|
|Seattle Children's Hospital||Seattle, Washington 98105|
|Kaiser Permanente-Oakland||Oakland, California 94611|
|New York University Langone Medical Center||New York, New York 10016|
|Columbia University Medical Center||New York, New York 10032|
|University of Minnesota Medical Center-Fairview||Minneapolis, Minnesota 55455|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|
|UMDNJ - Robert Wood Johnson University Hospital||New Brunswick, New Jersey 08903|
|Miller Children's Hospital||Long Beach, California 90806|
|Childrens Hospital of Orange County||Orange, California 92868-3874|
|Saint Joseph Children's Hospital of Tampa||Tampa, Florida 33607|
|Children's Healthcare of Atlanta - Egleston||Atlanta, Georgia 30322|
|The Childrens Mercy Hospital||Kansas City, Missouri 64108|
|Children's Hospital Colorado||Aurora, Colorado 80045|
|Lucile Packard Children's Hospital Stanford University||Palo Alto, California 94304|
|University of California San Francisco Medical Center-Parnassus||San Francisco, California 94143|