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Blinatumomab in Treating Younger Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02101853
First received: March 28, 2014
Last updated: October 10, 2014
Last verified: April 2014
  Purpose

This randomized phase III trial compares how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Monoclonal antibodies, such as blinatumomab, can block cancer growth by finding cancer cells and helping to kill them or carrying cancer-killing substances to them. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia.


Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Drug: dexamethasone
Drug: vincristine sulfate
Drug: pegaspargase
Drug: mitoxantrone hydrochloride
Drug: methotrexate
Drug: therapeutic hydrocortisone
Drug: cytarabine
Drug: leucovorin calcium
Drug: cyclophosphamide
Drug: etoposide
Drug: asparaginase
Procedure: allogeneic hematopoietic stem cell transplantation
Biological: blinatumomab
Drug: mercaptopurine
Drug: thioguanine
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 2-year DFS of HR and IR relapse patients [ Time Frame: From start of Block 2 of therapy to event (treatment failure, relapse, second malignancy, death) or last follow-up for those who are event-free, assesses at 2 years ] [ Designated as safety issue: No ]
  • 3-year DFS of LR relapse patients [ Time Frame: From start of Block 3 of therapy to first event (relapse, second malignant neoplasm, remission death) or last followup for those who are event-free, assessed at 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rates of MRD positivity (> 0.01%) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Will be compared at the end of Block 2 and 3 between randomized arms for HR and IR relapse patients.

  • Morphologic CR rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • MRD negativity (< 0.01%) rate [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Will be compared at the end of Block 2 and 3 between randomized arms for HR and IR relapse patients.

  • Proportion of patients that proceed to HSCT after treatment with blinatumomab (for treatment failure patients not previously receiving blinatumomab) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Feasibility of rapid taper of immune suppression for subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no aGVHD defined as < 25% rate of grade III-IV aGVHD [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The observed rates of grade III-IV aGVHD among this subset will be calculated with 95% confidence intervals and compared descriptively to target rates.

  • Safety of rapid taper of immune suppression for subset of HSCT patients with MRD >= 0.01% pre- and/or post-HSCT with no aGVHD defined as < 5% rate of treatment-related mortality (TRM) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The observed rates of TRM among this subset will be calculated with 95% confidence intervals and compared descriptively to target rates.


Estimated Enrollment: 438
Study Start Date: April 2014
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A (HR and IR control)
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT.
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
Drug: methotrexate
Given IT, IV, and PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: cytarabine
Given IT and IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic HSCT
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Experimental: Arm B (HR and IR blinatumomab)
Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: methotrexate
Given IT, IV, and PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: cytarabine
Given IT and IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic HSCT
Biological: blinatumomab
Given IV
Other Names:
  • anti-CD19/anti-CD3 recombinant bispecific monoclonal antibody MT103
  • bispecific T-cell engager MT103
  • MEDI-538
  • MT-103
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Active Comparator: Arm C (LR control)
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT, IV, and PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: cytarabine
Given IT and IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: asparaginase
Given IM
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: thioguanine
Given PO
Other Name: 6-TG
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Experimental: Arm D (LR blinatumomab)
Patients receive Block 2 over 4 weeks, Blinatumomab Block 2 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Block 3 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Block 3 over 5 weeks, and then Maintenance.
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT, IV, and PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: therapeutic hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: cytarabine
Given IT and IV or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: leucovorin calcium
Given IV or PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Biological: blinatumomab
Given IV
Other Names:
  • anti-CD19/anti-CD3 recombinant bispecific monoclonal antibody MT103
  • bispecific T-cell engager MT103
  • MEDI-538
  • MT-103
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: thioguanine
Given PO
Other Name: 6-TG
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • First relapse of B-ALL with or without extramedullary disease
  • No waiting period for patients who relapse while receiving standard maintenance therapy
  • Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy
  • Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Stem cell transplant or rescue: patients with prior stem cell transplant or rescue are not eligible for this study
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 to < 2 years: =< 0.6 mg/dL
    • 2 to < 6 years: =< 0.8 mg/dL
    • 6 to < 10 years: =< 1 mg/dL
    • 10 to < 13 years: =< 1.2 mg/dL
    • Females >= 14 years: =< 1.4 mg/dL
    • Males 13 to < 16 years: =< 1.5 mg/dL
    • Males >= 16 years: =< 1.7 mg/dL
  • Direct bilirubin < 3.0 mg/dL
  • Shortening fraction of >= 27% by echocardiogram, or
  • Ejection fraction of >= 50% by radionuclide angiogram

Exclusion Criteria:

  • Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL
  • Burkitt leukemia/lymphoma
  • T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL)
  • B-lymphoblastic lymphoma (B-LL)
  • Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
  • Patients with a known concomitant genetic syndrome, including Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
  • Patients with known human immunodeficiency virus (HIV) infection
  • Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos)
  • Patients who have had prior treatment with blinatumomab
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants
  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
  • Sexually active patients of reproductive potential who do not agree to use an effective contraceptive method for the duration of their study participation
  • Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: seizure disorder that has required prolonged (at least 4 weeks) of continuous treatment with an antiepileptic drug within the last year, history of cerebrovascular ischemia/hemorrhage, history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination /movement disorder, or autoimmune disease with CNS involvement
  • Pre-randomization R1 and R2: interval development of significant central nervous system pathology that would preclude treatment with blinatumomab
  • Pre-hematopoietic stem cell transplant (HSCT): interval development of significant pathology that would preclude HSCT including the following infectious and organ system pathologies:

    • Infections: patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded
    • Patients acquiring fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of active disease remaining by computed tomography (CT) evaluation
    • Organ function requirements for HSCT: must meet the criteria for renal, biliary and cardiac function as outlined above; in addition, must have adequate pulmonary function defined as a forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) >= 60% by pulmonary function tests (PFTs)
    • For children who are unable to cooperate for PFTs, the criteria are: no evidence of dyspnea at rest, no exercise intolerance, and not requiring supplemental oxygen therapy
  • All patients and/or their parent or legal guardian must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
  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: NCT02101853

Locations
United States, Pennsylvania
Children's Oncology Group Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Patrick A. Brown    410-614-4915    pbrown@jhmi.edu   
Principal Investigator: Patrick A. Brown         
Sponsors and Collaborators
Investigators
Principal Investigator: Patrick Brown Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02101853     History of Changes
Other Study ID Numbers: NCI-2014-00631, NCI-2014-00631, COG-AALL1331, AALL1331, AALL1331, U10CA180886, U10CA098543
Study First Received: March 28, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Burkitt Lymphoma
Leukemia
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases
6-Mercaptopurine
Antibodies, Bispecific
Asparaginase
Cortisol succinate
Cyclophosphamide
Cytarabine
Dexamethasone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate

ClinicalTrials.gov processed this record on November 20, 2014