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

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ClinicalTrials.gov Identifier: NCT01700946
Recruitment Status : Active, not recruiting
First Posted : October 4, 2012
Last Update Posted : July 21, 2020
Sponsor:
Collaborators:
Cookies for Kids' Cancer
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Recurrent B-Cell Childhood Acute 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 Device: CliniMACS Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : April 15, 2013
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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

Cells for infusion are prepared using the CliniMACS System.

 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

Device: CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Name: Cell Selection System
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

Cells for infusion are prepared using the CliniMACS System.

 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

Device: CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Name: Cell Selection System


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    Estimate the 3-year survival rate of participants with first relapse or primary refractory precursor B-cell ALL treated with risk-directed therapy.

  2. 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 ]
    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 :
  1. Proportion of participants with positive minimal residual disease [ Time Frame: At 3 months after the on-study date of the last enrolled patient ]
    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.

  2. Mean of CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ]
    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.

  3. Median CD20 expression levels [ Time Frame: approximately 5 weeks after the on-study date of the last enrolled patient ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
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 peripheral blood, OR
    2. Refractory to one or two courses of frontline induction therapy (≥ 5% blasts in the bone marrow or peripheral blood 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: Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is > ULN, 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 1.2 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 defined as DNA index ≥1.16 or modal chromosome number ≥51, 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01700946


Locations
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United States, California
Rady Children's Hospital and Health Center
San Diego, California, United States, 92123
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Sponsors and Collaborators
St. Jude Children's Research Hospital
Cookies for Kids' Cancer
Assisi Foundation
Investigators
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Principal Investigator: Sima Jeha, MD St. Jude Children's Research Hospital
More Information
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Additional Information:

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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01700946    
Other Study ID Numbers: ALLR18
NCI-2012-00587 ( Registry Identifier: NCi Clinical Trial Registration Program )
First Posted: October 4, 2012    Key Record Dates
Last Update Posted: July 21, 2020
Last Verified: July 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by St. Jude Children's Research Hospital:
leukemia
lymphoma
Non-Hodgkins
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Aldesleukin
Dexamethasone
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
 Hydrocortisone acetate
Hydrocortisone hemisuccinate
Cyclophosphamide
Rituximab
Methotrexate
Etoposide
Vincristine
Interleukin-2
Asparaginase
Mercaptopurine
Mitoxantrone
Clofarabine
Vinblastine
Pegaspargase
Teniposide