Chemoimmunotherapy With Epratuzumab in Relapsed Acute Lymphoblastic Leukemia (ALL)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00098839
First received: December 8, 2004
Last updated: March 24, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Recurrent Childhood Acute Lymphoblastic Leukemia
Drug: L-asparaginase
Drug: doxorubicin hydrochloride
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Biological: epratuzumab
Drug: cytarabine
Drug: prednisone
Drug: pegaspargase
Drug: dexrazoxane hydrochloride
Drug: methotrexate
Drug: etoposide
Drug: cyclophosphamide
Drug: leucovorin calcium
Biological: filgrastim
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Feasibility Pilot and Phase II Study Of Chemoimmunotherapy With Epratuzumab (IND #12034) for Children With Relapsed CD22-Positive Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Remission Re-induction (CR2) Rate [ Time Frame: At the end of Block 1 of re-induction therapy (day 36) ] [ Designated as safety issue: No ]
    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.

  • Event-free Survival Rate [ Time Frame: At 4 months after enrollment ] [ Designated as safety issue: No ]
    Proportion of patients who were event free at 4 months

  • Rate of Minimal Residual Disease (MRD) < 0.01% [ Time Frame: At the end of Block 1 of re-induction therapy (day 36) ] [ Designated as safety issue: No ]
    Proportion of patients (evaluable and had MRD measured at the end of Block 1) who had MRD < 0.01%.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Up to day 36 ] [ Designated as safety issue: No ]
    Determined along with the mean, median, standard deviation and range of the parameters of interest. Statistical analysis will be purely descriptive.


Enrollment: 134
Study Start Date: February 2005
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: L-asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: therapeutic hydrocortisone
40 mg/m2/day PO divided BID or TID
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Biological: epratuzumab
Given IV
Other Names:
  • AMG 412
  • LL2
  • MOAB LL2
  • monoclonal antibody LL2
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Experimental: 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.
Drug: L-asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: therapeutic hydrocortisone
40 mg/m2/day PO divided BID or TID
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Biological: epratuzumab
Given IV
Other Names:
  • AMG 412
  • LL2
  • MOAB LL2
  • monoclonal antibody LL2
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: dexrazoxane hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Savene
  • Totect
  • Zinecard
Drug: methotrexate
Given IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 31 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098839

  Show 46 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Elizabeth Raetz, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00098839     History of Changes
Other Study ID Numbers: ADVL04P2, NCI-2011-01624, COG-ADVL04P2, CDR0000396777, U10CA098543
Study First Received: December 8, 2004
Results First Received: March 3, 2015
Last Updated: March 24, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Asparaginase
Cortisol succinate
Cyclophosphamide
Cytarabine
Dexrazoxane
Doxorubicin
Etoposide
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Leucovorin
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Pegaspargase
Prednisone
Razoxane
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on August 04, 2015