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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 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: February 26, 2015
Last verified: December 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
Adult B Acute Lymphoblastic Leukemia
Childhood B 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:
  • 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 up to 10 years ] [ Designated as safety issue: No ]
  • 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 follow-up for those who are event-free, assessed up to 10 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: 598
Study Start Date: December 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 Name: DM
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar
Drug: Pegaspargase
Given IV
Other Names:
  • Oncaspar
  • PEGLA
Drug: Mitoxantrone Hydrochloride
Given IV
Drug: Methotrexate
Given IT, IV, and PO
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Cetacort
  • HC
Drug: Cytarabine
Given IT and IV or SC
Other Names:
  • CHX-3311
  • U-19920
Drug: Leucovorin Calcium
Given IV or PO
Other Name: CF
Drug: Cyclophosphamide
Given IV
Drug: Etoposide
Given IV
Other Name: Lastet
Drug: Asparaginase
Given IM
Other Names:
  • MK-965
  • Re-82-TAD-15
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
  • HSC
  • HSCT
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
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 Name: DM
Drug: Methotrexate
Given IT, IV, and PO
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Cetacort
  • HC
Drug: Cytarabine
Given IT and IV or SC
Other Names:
  • CHX-3311
  • U-19920
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Other Names:
  • HSC
  • HSCT
Biological: Blinatumomab
Given IV
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
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 Name: DM
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar
Drug: Pegaspargase
Given IV
Other Names:
  • Oncaspar
  • PEGLA
Drug: Methotrexate
Given IT, IV, and PO
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Cetacort
  • HC
Drug: Cytarabine
Given IT and IV or SC
Other Names:
  • CHX-3311
  • U-19920
Drug: Leucovorin Calcium
Given IV or PO
Other Name: CF
Drug: Cyclophosphamide
Given IV
Drug: Etoposide
Given IV
Other Name: Lastet
Drug: Asparaginase
Given IM
Other Names:
  • MK-965
  • Re-82-TAD-15
Drug: Mercaptopurine
Given PO
Drug: Thioguanine
Given PO
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
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 Name: DM
Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar
Drug: Pegaspargase
Given IV
Other Names:
  • Oncaspar
  • PEGLA
Drug: Methotrexate
Given IT, IV, and PO
Drug: Therapeutic Hydrocortisone
Given IT
Other Names:
  • Aeroseb-HC
  • Cetacort
  • HC
Drug: Cytarabine
Given IT and IV or SC
Other Names:
  • CHX-3311
  • U-19920
Drug: Leucovorin Calcium
Given IV or PO
Other Name: CF
Drug: Cyclophosphamide
Given IV
Drug: Etoposide
Given IV
Other Name: Lastet
Biological: Blinatumomab
Given IV
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • MEDI-538
  • MT-103
Drug: Mercaptopurine
Given PO
Drug: Thioguanine
Given PO
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
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
  • Patient has not had prior treatment with blinatumomab
  • 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:

  • Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible
  • Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible
  • Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible
  • Patients with B-lymphoblastic lymphoma (B-LL) are not eligible
  • 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 known to have one of the following concomitant genetic syndromes: 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)
  • Lactating females who plan to breastfeed
  • Patients who are pregnant; pregnancy test is required for female patients of childbearing potential
  • Sexually active patients of reproductive potential who have not agreed 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: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination /movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved)
  • Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)
  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

  Show 22 Study Locations
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: February 26, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Bispecific
Antibodies, Monoclonal
Cortisol succinate
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Mitoxantrone
Analgesics
Anti-Inflammatory Agents
Antineoplastic Agents
Central Nervous System Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on February 27, 2015