MedPath

Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)

Registration Number
NCT00098839
Lead Sponsor
Children's Oncology Group
Brief Summary

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.

Detailed Description

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
134
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

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyvincristine sulfateEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyleucovorin calciumEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklytherapeutic hydrocortisoneFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyepratuzumabFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklytherapeutic hydrocortisoneEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyvincristine sulfateFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklydexrazoxane hydrochlorideFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyetoposideFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyprednisoneFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyleucovorin calciumFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyfilgrastimFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyepratuzumabEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklydexrazoxane hydrochlorideEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyfilgrastimEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklydoxorubicin hydrochlorideFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklyL-asparaginaseFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklycytarabineFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklymethotrexateFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklypegaspargaseFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab once weeklycyclophosphamideFour 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyL-asparaginaseEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklydoxorubicin hydrochlorideEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklycytarabineEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyprednisoneEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklypegaspargaseEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklymethotrexateEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklyetoposideEight 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.
Reinduction Chemoimmunotherapy with Epratuzumab twice weeklycyclophosphamideEight 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.
Primary Outcome Measures
NameTimeMethod
Event-free Survival RateAt 4 months after enrollment

Proportion of patients who were event free at 4 months

Remission Re-induction (CR2) RateAt the end of Block 1 of re-induction therapy (day 36)

The proportion of patients who achieved complete response at the end Block 1 of re-induction therapy. Complete Remission (CR) - Attainment of M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (ANC \>1000/uL and platelet count \>100,000/uL). Partial Remission (PR) - Complete disappearance of circulating blasts and achievement of M2 marrow status (5% or \< 25% blast cells and adequate cellularity). Partial Remission Cytolytic (PRCL) - Complete disappearance of circulating blasts and achievement of at least 50% reduction from baseline in bone marrow blast count. Minimal Response Cytolytic (MRCL) - 50% reduction in the peripheral blast count with no increase in peripheral white blood cell count.

Rate of Minimal Residual Disease (MRD) < 0.01%At the end of Block 1 of re-induction therapy (day 36)

Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD \< 0.01%.

Secondary Outcome Measures
NameTimeMethod
PharmacokineticsUp to day 36

Mean trough serum concentration measured before final dose of epratuzumab.

Trial Locations

Locations (46)

Indiana University Medical Center

🇺🇸

Indianapolis, Indiana, United States

M D Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

University of California San Francisco Medical Center-Parnassus

🇺🇸

Frisco, California, United States

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

David Geffen School of Medicine at UCLA

🇺🇸

Los Angeles, California, United States

Loma Linda University Medical Center

🇺🇸

Loma Linda, California, United States

Kaiser Permanente-Oakland

🇺🇸

Oakland, California, United States

Miller Children's Hospital

🇺🇸

Long Beach, California, United States

Children's Hospital Central California

🇺🇸

Madera, California, United States

Lucile Packard Children's Hospital Stanford University

🇺🇸

Palo Alto, California, United States

Childrens Hospital of Orange County

🇺🇸

Orange, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Saint Joseph Children's Hospital of Tampa

🇺🇸

Tampa, Florida, United States

Children's Healthcare of Atlanta - Egleston

🇺🇸

Atlanta, Georgia, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Wayne State University

🇺🇸

Detroit, Michigan, United States

The Childrens Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

New York University Langone Medical Center

🇺🇸

New York, New York, United States

University of New Mexico Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Columbia University Medical Center

🇺🇸

New York, New York, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Midwest Children's Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

The Children's Hospital at Westmead

🇦🇺

Sydney, New South Wales, Australia

San Jorge Children's Hospital

🇵🇷

Santurce, Puerto Rico

University of Minnesota Medical Center-Fairview

🇺🇸

Minneapolis, Minnesota, United States

Vanderbilt-Ingram Cancer Center

🇺🇸

Nashville, Tennessee, United States

Primary Children's Medical Center

🇺🇸

Salt Lake City, Utah, United States

Princess Margaret Hospital for Children

🇦🇺

Perth, Western Australia, Australia

University of Rochester

🇺🇸

Rochester, New York, United States

University of Kentucky

🇺🇸

Lexington, Kentucky, United States

C S Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Tulane University Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Eastern Maine Medical Center

🇺🇸

Bangor, Maine, United States

UMDNJ - Robert Wood Johnson University Hospital

🇺🇸

New Brunswick, New Jersey, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

Hospital Sainte-Justine

🇨🇦

Montreal, Quebec, Canada

Newark Beth Israel Medical Center

🇺🇸

Newark, New Jersey, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

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