Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)
NCT ID: NCT00098839
Last Updated: 2017-12-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
134 participants
INTERVENTIONAL
2005-02-28
2011-04-30
Brief Summary
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Detailed Description
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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.
IV. To estimate the remission re-induction rate and four-month event-free survival (EFS) for patients with early first relapse ALL who receive epratuzumab in combination with cytotoxic thermotherapy.
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. A Simon's two stage design was initially used to evaluate the efficacy of the once weekly dosing schedule for part B patients (called B1 cohort), which planned to accrue a total of 112 patients with 56 to be enrolled at the first stage. After completion the accrual of stage 1, i.e. after 56 patients were enrolled, the design of part B was revised to evaluate a modified doing schedule (twice weekly doing, called B2 cohort) using a stratified two-stage design by London and Chang (2005), where patients enrolled to B2 were stratified according to relapse (first early marrow relapsed occurring \< 18 months from initial diagnosis vs 18-36 months from initial diagnosis).
PART A (CLOSED TO ACCRUAL 10/30/06):
REDUCTION THERAPY: Patients receive epratuzumab IV over several hours 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) did not receive this first dose of IT cytarabine.
RE-INDUCTION THERAPY (BLOCK 1): Patients received 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 received 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 received etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 1-5. Patients also received high-dose methotrexate IV continuously over 24 hours on day 22. Beginning 42 hours after the start of the methotrexate infusion (day 24), patients received 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 received 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 received cytarabine IV over 3 hours twice daily on days 1, 2, 8, and 9 and native E. Coli asparaginase IM on days 2 and 9. Patients receive G-CSF SC once daily beginning on day 10 and continuing until blood counts recovered.
PART B:
RE-INDUCTION THERAPY (BLOCK 1): Patients received vincristine, prednisone, pegaspargase, doxorubicin, cytarabine, methotrexate, and epratuzumab as in phase I re-induction therapy (block 1). Epratuzumab was given on Days 1, 8, 15 and 22 before amendment 5 (B1 cohort) and on Days 1, 4, 8, 11, 15, 18, 22 and 25 after amendment 5 (B2 cohort) Patients with CNS-negative disease received methotrexate IT on days 1 and 22. Patients with CNS-positive disease received triple IT therapy comprising methotrexate, cytarabine, and hydrocortisone on days 8, 15, 22, and 29.
RE-INDUCTION THERAPY (BLOCKS 2 AND 3): Patients received 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.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Reinduction Chemoimmunotherapy with Epratuzumab once weekly
Four weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 8, 15, 22. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy.
L-asparaginase
Given IM
doxorubicin hydrochloride
Given IV
therapeutic hydrocortisone
40 mg/m2/day PO divided BID or TID
vincristine sulfate
Given IV
epratuzumab
Given IV
cytarabine
Given IT
prednisone
Given orally
pegaspargase
Given IM
dexrazoxane hydrochloride
Given IV
methotrexate
Given IT
etoposide
Given IV
cyclophosphamide
Given IV
leucovorin calcium
Given IV
filgrastim
Given SC
Reinduction Chemoimmunotherapy with Epratuzumab twice weekly
Eight 8 twice-weekly doses of epratuzumab (360 mg/m2/dose) IV days 1, 4, 8, 11, 15, 18, 22 \& 25. Also received vincristine sulfate, prednisone, pegaspargase, doxorubicin hydrochloride, dexrazoxane hydrochloride, etoposide, cyclophosphamide, filgrastim, high-dose (HD) methotrexate with Leucovorin calcium rescue, L-asparaginase, cytarabine, IT cytarabine, IT methotrexate (CNS-negative), Intrathecal triple therapy (ITT) (methotrexate, cytarabine, therapeutic hydrocortisone for CNS-positive) during the 3 blocks of reinduction therapy.
L-asparaginase
Given IM
doxorubicin hydrochloride
Given IV
therapeutic hydrocortisone
40 mg/m2/day PO divided BID or TID
vincristine sulfate
Given IV
epratuzumab
Given IV
cytarabine
Given IT
prednisone
Given orally
pegaspargase
Given IM
dexrazoxane hydrochloride
Given IV
methotrexate
Given IT
etoposide
Given IV
cyclophosphamide
Given IV
leucovorin calcium
Given IV
filgrastim
Given SC
Interventions
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L-asparaginase
Given IM
doxorubicin hydrochloride
Given IV
therapeutic hydrocortisone
40 mg/m2/day PO divided BID or TID
vincristine sulfate
Given IV
epratuzumab
Given IV
cytarabine
Given IT
prednisone
Given orally
pegaspargase
Given IM
dexrazoxane hydrochloride
Given IV
methotrexate
Given IT
etoposide
Given IV
cyclophosphamide
Given IV
leucovorin calcium
Given IV
filgrastim
Given SC
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* At least 25% expression of CD22 by immunophenotyping
* In marrow relapse (M3 bone marrow) with or without associated extramedullary disease as defined by 1 of the following:
* In first or later marrow relapse occurring any time after initial diagnosis (part A \[closed to accrual as of 10/30/06\] or B)
* In first, early marrow relapse with or without associated extramedullary disease occurring \< 36 months from the time of initial diagnosis (part B only)
* No B-cell L3 morphology OR evidence of a regulator gene that codes for a transcription factor (MYC) translocation by molecular or cytogenetic analysis
* No Down syndrome
* Patients with CNS or other extramedullary site involvement are allowed
* Performance status - Karnofsky 50-100% (for patients \> 10 years of age)
* Performance status - Lansky 50-100% (for patients ≤ 10 years of age)
* White Blood Count (WBC) ≤ 50,000/mm\^3 (part A only \[closed to accrual as of 10/30/06\])
* Bilirubin ≤ 1.5 times upper limit of normal unless disease-related (ULN)
* Alanine aminotransferase (ALT) ≤ 5 times ULN
* Albumin ≥ 2 g/dL
* Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min
* Creatinine as defined by age as follows:
* ≤ 0.5 mg/dL (for patients \< 1 year old)
* ≤ 0.8 mg/dL (for patients 1 to 5 years old)
* ≤ 1.0 mg/dL (for patients 6 to 10 years old)
* ≤ 1.2 mg/dL (for patients 11 to 15 years old)
* ≤ 1.5 mg/dL (for patients \> 15 years old)
* Shortening fraction ≥ 27% by echocardiogram
* Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA)
* No dyspnea at rest
* No exercise intolerance
* Pulse oximetry \> 94%
* No active or uncontrolled infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Recovered from prior immunotherapy
* At least 4 months since prior stem cell transplantation or rescue AND no evidence of active graft-vs-host disease
* At least 7 days since prior hematopoietic growth factors
* At least 7 days since prior biologic therapy\*
* No other concurrent immunotherapy
* No other concurrent biologic therapy
* Recovered from prior chemotherapy
* No waiting period for children who relapse while receiving standard ALL maintenance therapy
* No prior cumulative anthracycline exposure \> 400 mg/m\^2\*
* No concurrent chemotherapy
* Recovered from prior radiotherapy
* No concurrent radiotherapy
* At least 2 days since prior hydroxyurea
* No other concurrent investigational drugs
* No other concurrent anticancer agents
2 Years
31 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Elizabeth Raetz, MD
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Miller Children's Hospital
Long Beach, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
Childrens Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
University of California San Francisco Medical Center-Parnassus
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Saint Joseph Children's Hospital of Tampa
Tampa, Florida, United States
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States
Indiana University Medical Center
Indianapolis, Indiana, United States
University of Kentucky
Lexington, Kentucky, United States
Tulane University Health Sciences Center
New Orleans, Louisiana, United States
Eastern Maine Medical Center
Bangor, Maine, United States
Johns Hopkins University
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Wayne State University
Detroit, Michigan, United States
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Childrens Mercy Hospital
Kansas City, Missouri, United States
UMDNJ - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Newark Beth Israel Medical Center
Newark, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
New York University Langone Medical Center
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
Primary Children's Medical Center
Salt Lake City, Utah, United States
Seattle Children's Hospital
Seattle, Washington, United States
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead
Sydney, New South Wales, Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Hospital Sainte-Justine
Montreal, Quebec, Canada
San Jorge Children's Hospital
Santurce, , Puerto Rico
Countries
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Other Identifiers
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NCI-2011-01624
Identifier Type: REGISTRY
Identifier Source: secondary_id
COG-ADVL04P2
Identifier Type: OTHER
Identifier Source: secondary_id
CDR0000396777
Identifier Type: OTHER
Identifier Source: secondary_id
ADVL04P2
Identifier Type: -
Identifier Source: org_study_id