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Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma

This study is currently recruiting participants.
Verified April 2013 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Cookies for Kids' Cancer
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01700946
First received: October 1, 2012
Last updated: April 22, 2013
Last verified: April 2013
History of Changes
  Purpose

The overall objective of this protocol is to improve the cure rate of relapsed precursor B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma.

This phase II trial is studying risk-directed therapy for B-lymphoblastic leukemia or lymphoma in first relapse. Standard risk (SR) and high risk (HR) participants will receive different therapy. Treatment will consist of chemotherapy for SR participants, and chemotherapy followed by hematopoietic stem cell transplant (HSCT) for HR in first relapse. Induction therapy consists of three blocks of chemotherapy. The first block is a novel immunotherapy regimen that includes chemotherapy, rituximab and infusion of haploidentical natural killer (NK) cells. SR participants will continue to receive chemotherapy for a total duration of approximately 2 years. HR participants will be candidates for HSCT and will proceed to transplant once a suitable donor is found and their minimal residual disease (MRD) is negative.


Condition Intervention Phase
Recurrent Childhood Acute B-lymphoblastic Leukemia
Recurrent Childhood B-lymphoblastic Lymphoma
 Drug: dexamethasone
Drug: vincristine sulfate
Biological: rituximab
Drug: clofarabine
Drug: cyclophosphamide
Drug: etoposide
Biological: aldesleukin
Drug: pegaspargase
Drug: methotrexate
Drug: mercaptopurine
Drug: cytarabine
Drug: mitoxantrone
Drug: teniposide
Drug: vinblastine
Biological: natural killer cell infusion
Other: laboratory biomarker analysis
Drug: therapeutic hydrocortisone
Procedure: allogeneic hematopoietic stem cell transplantation
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 3-year overall survival rate of patients with relapsed ALL [ Time Frame: At 3 years of follow-up since the on-study date of the last enrolled patient ] [ Designated as safety issue: No ]
    Estimate the 3-year survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy.

  • 3-year event-free survival rates in patients with relapsed ALL [ Time Frame: At 3 years of follow-up since the on-study date of the last enrolled patient ] [ Designated as safety issue: No ]
    Estimate the 3-year event-free survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy.


Secondary Outcome Measures:
  • Proportion of participants with positive minimal residual disease [ Time Frame: At 3 months after the on-study date of the last enrolled patient ] [ Designated as safety issue: No ]
    To determine minimal residual disease (MRD) levels at the end of remission induction therapy for participants with relapsed precursor B-cell ALL and compare the results with those in protocol ALLR17.

  • Mean of CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ] [ Designated as safety issue: No ]
    To estimate mean levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block 1 of remission induction therapy for relapsed precursor B-cell ALL.

  • Median CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ] [ Designated as safety issue: No ]
    To estimate median levels of CD20 expression at baseline, during treatment with dexamethasone-containing chemotherapy and following rituximab treatment in Block 1 of remission induction therapy for relapsed precursor B-cell ALL.


Estimated Enrollment: 40
Study Start Date: October 2012
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard Risk
Interventions: dexamethasone, vincristine sulfate, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, teniposide, vinblastine, natural killer cell infusion, laboratory biomarker analysis, therapeutic hydrocortisone
 Drug: dexamethasone
given intravenously or orally
Other Name: Decadron(R)
Drug: vincristine sulfate
given intravenously
Other Name: Oncovin(R)
Biological: rituximab
given intravenously
Other Name: Rituxan(R)
Drug: clofarabine
given intravenously
Other Names:
  • Clolar(TM)
  • clofarex
Drug: cyclophosphamide
given intravenously
Other Name: Cytoxan(R)
Drug: etoposide
given intravenously
Other Names:
  • VP-16
  • Vepesid(R)
Biological: aldesleukin
given subcutaneously
Other Names:
  • IL-2
  • interleukin-2
  • Proleukin (R)
Drug: pegaspargase
given intravenously
Other Names:
  • PEG-ASP
  • Peg-L-asparaginase
  • PEG-asparaginase
  • Oncaspar(R)
Drug: methotrexate
given intrathecally or intravenously
Other Names:
  • MTX
  • HDMTX
Drug: mercaptopurine
given orally
Other Names:
  • 6-MP
  • Purinethol(R)
Drug: cytarabine
given intrathecally or intravenously
Other Names:
  • Ara-C
  • Cytosar-U(R)
Drug: mitoxantrone
given intravenously
Other Name: Novantrone(R)
Drug: teniposide
given intravenously
Other Names:
  • VM-26
  • Vumon(R)
Drug: vinblastine
given intravenously
Other Name: Velban(R)
Biological: natural killer cell infusion
undergo allogeneic natural killer cell infusion
Other Name: NK cell infusion
Other: laboratory biomarker analysis
correlative studies
Drug: therapeutic hydrocortisone
given intrathecally
Other Name: Cortef
Active Comparator: High Risk
Interventions: dexamethasone, vincristine, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, natural killer cell infusion, allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis, therapeutic hydrocortisone
 Drug: dexamethasone
given intravenously or orally
Other Name: Decadron(R)
Drug: vincristine sulfate
given intravenously
Other Name: Oncovin(R)
Biological: rituximab
given intravenously
Other Name: Rituxan(R)
Drug: clofarabine
given intravenously
Other Names:
  • Clolar(TM)
  • clofarex
Drug: cyclophosphamide
given intravenously
Other Name: Cytoxan(R)
Drug: etoposide
given intravenously
Other Names:
  • VP-16
  • Vepesid(R)
Biological: aldesleukin
given subcutaneously
Other Names:
  • IL-2
  • interleukin-2
  • Proleukin (R)
Drug: pegaspargase
given intravenously
Other Names:
  • PEG-ASP
  • Peg-L-asparaginase
  • PEG-asparaginase
  • Oncaspar(R)
Drug: methotrexate
given intrathecally or intravenously
Other Names:
  • MTX
  • HDMTX
Drug: mercaptopurine
given orally
Other Names:
  • 6-MP
  • Purinethol(R)
Drug: cytarabine
given intrathecally or intravenously
Other Names:
  • Ara-C
  • Cytosar-U(R)
Drug: mitoxantrone
given intravenously
Other Name: Novantrone(R)
Biological: natural killer cell infusion
undergo allogeneic natural killer cell infusion
Other Name: NK cell infusion
Other: laboratory biomarker analysis
correlative studies
Drug: therapeutic hydrocortisone
given intrathecally
Other Name: Cortef
Procedure: allogeneic hematopoietic stem cell transplantation
undergo allogeneic HSCT
Other Name: HSCT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Must have relapsed or refractory precursor B-cell acute lymphoblastic leukemia or acute lymphoblastic lymphoma.

  • Participants with leukemia must meet one of the following:

    1. In first hematologic relapse, defined as the reappearance (in a patient who has previously achieved remission) of leukemia blasts in the bone marrow, OR
    2. Refractory to one or two courses of frontline induction therapy (≥ 5% blasts in the bone marrow confirmed by flow cytometric analysis).

  • Participant with lymphoma must meet one of the following:

    1. In first relapse, OR

    2. Refractory to one or two courses of frontline induction therapy with measurable disease

      • Should flow cytometric analyses suggest relapse (by the reappearance of a similar immunophenotype to the original leukemia) in the presence of <5% blasts morphologically, a repeat bone marrow test is recommended to confirm relapse.
      • Molecular or genetic relapse is characterized by the reappearance of a cytogenetic or molecular abnormality.
      • Early relapse is defined as relapse on therapy or < 6 months after completion of frontline therapy. Late relapse is defined as relapse occurring ≥ 6 months after completion of frontline therapy.
  • Participant's age is < 22 years at time of enrollment (e.g. participant is eligible until 22nd birthday).

  • Prior therapy:

    1. There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy.
    2. Emergent radiation therapy, one dose of intrathecal chemotherapy, and up to 7 days of steroids for treatment of relapse are permitted before start of treatment in participants who relapse after completion of frontline therapy.
    3. At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for a minimum of 2 weeks, if applicable. Participants with ALL or NHL who were transplanted in first remission are eligible for this study.

Organ function requirements

  • Hepatic: Serum direct bilirubin < 1.4 mg/dl
  • Cardiac: Shortening fraction > 28%

  • Renal: Glomerular filtration rate >50cc/min/1.73 m^2, OR maximum serum creatinine (SC) based on age as follows:

    • If age is 1 to 2 years, then maximum SC is 0.6 mg/dL
    • If age is 2 to 6 years, then maximum SC is 0.8 mg/dL
    • If age is 6 to 10 years, then maximum SC is 1 mg/dL
    • If age is 10 to <13 years, then maximum SC is 1 mg/dL
    • If age is 13 to 16 years, then maximum SC is 1.5 mg/dL for males and 1.4 mg/dL for females
    • If age is >16 years, then maximum SC is 1.7 mg/dL for males and 1.4 mg/dL for females

EXCLUSION CRITERIA:

  • Leukemia participants ages 1 to 5 years with induction failure AND favorable cytogenetics (i.e., hyperdiploidy or ETV6-RUNXI).
  • Hepatitis B or HIV infection.
  • Pregnant or breast-feeding
  • Inability or unwillingness or research participant or legal guardian/representative to give written informed consent.

INCLUSION CRITERIA FOR NK CELL DONORS:

  • Donor is at least 18 years of age.
  • Donor is a family member.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700946

Contacts
Contact: Deepa Bhojwani, MD 866-278-5833

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Deepa Bhojwani, MD     866-278-5833     info@stjude.org    
Principal Investigator: Deepa Bhojwani, MD            
Sponsors and Collaborators
St. Jude Children's Research Hospital
Cookies for Kids' Cancer
Investigators
Principal Investigator: Deepa Bhojwani, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
St. Jude Children's Research Hospital  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01700946     History of Changes
Other Study ID Numbers: ALLR18
Study First Received: October 1, 2012
Last Updated: April 22, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
leukemia
lymphoma
Non-Hodgkins

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
6-Mercaptopurine
Cytarabine
Methotrexate
Cyclophosphamide
Teniposide
Etoposide phosphate
Pegaspargase
Clofarabine
Aldesleukin
Rituximab
Asparaginase

ClinicalTrials.gov processed this record on May 23, 2013