Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase IBiomarker/Laboratory analysis, TreatmentClosed2 to 31NCI, OtherADVL04P2
NCI-2011-01624, COG-ADVL04P2, CDR0000396777, U10CA098543, NCT00098839

Trial Description


This Phase II trial is studying how well giving epratuzumab together with an established chemotherapy platform works in treating young patients with relapsed acute lymphoblastic leukemia. Monoclonal antibodies, such as epratuzumab, 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. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing them or by stopping them from dividing. Giving monoclonal antibody therapy in combination chemotherapy may kill cancer cells more effectively.

Further Study Information


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.


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).


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.


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.

Eligibility Criteria

Inclusion Criteria:

  • Diagnosis of B lymphoblastic leukemia (B-ALL)
  • 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

  • National Cancer Institute
Elizabeth Raetz, MD, Principal Investigator

Link to the current record.
NLM Identifier NCT00098839 processed this data on April 09, 2015

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to