ALLR18: Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma

A Phase II Study of Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma

Categories:

Leukemia / Lymphoma

Phase I/II

Diseases Treated:

Relapsed or refractory precursor B-cell acute lymphoblastic leukemia and lymphoma

Eligibility Overview:

  • B-cell acute lymphoblastic leukemia or lymphoblastic lymphoma that has:
    • Come back after treatment the first time
    • Did not respond to treatment the first time
  • Less than 22 years of age
  • Does not have HIV or hepatitis B infection
  1. 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 2 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.

    Primary Objective

    To estimate the 3-year survival rate of participants with first relapse or primary refractory precursor B-cell ALL and lymphoblastic lymphoma treated with risk-directed therapy.

    Trial Outline

    The general treatment plan will consist of chemotherapy for standard-risk participants and chemotherapy followed by hematopoietic stem cell transplant (HSCT) for high-risk participants in first relapse of B-precursor ALL or lymphoblastic lymphoma.

    Remission induction for all participants consists of 3 blocks of therapy, wherein the first block is a novel immunotherapy regimen that includes cytotoxic chemotherapy, rituximab and infusion of haploidentical natural killer (NK) cells.

    • Standard-risk patients will continue to receive chemotherapy for a total duration of approximately 2 years.
    • High-risk patients will be candidates for HSCT and will proceed to transplant once a suitable donor is found and the patient achieves negative MRD.

    Standard Risk

    • Late relapse (> or = 6 months after completion of frontline therapy) AND
    • Maximum residual disease (MRD) is <0.01% at the end of Block II or remission induction therapy.

    Provisional standard-risk participants (i.e., late relapse) will be re-assigned to high risk if MRD is > or = 0.01% at the end of Block II. Participants with lymphoma must be in complete remission at the end of Block III.

    High Risk (participants will meet one of the following criteria)

    • Early relapse (on therapy or <6 months after completion of frontline therapy), OR
    • Any relapse after hematopoietic stem cell transplant, OR
    • MRD > or = 0.01% at the end of Block II of remission induction therapy, OR
    • Re-emergence of MRD at any time after attaining negative MRD on this clinical trial

    Natural killer (NK) cell collection

    Donors who meet eligibility criteria will undergo apheresis once. The cells obtained will be purified for CD56+ cells utilizing the CliniMACS selection system. The NK cell product will undergo quality control testing following standard operating procedures of the St. Jude Human Applications Laboratory.

    After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 1 year, and then yearly for up to 10 years.

    Study Arms

    Active Comparator: Standard Risk

    Interventions

    • Drugs: Dexamethasone, vincristine sulfate, clofarabine, cyclophosphamide, etoposide, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, teniposide, vinblastine, therapeutic hydrocortisone
    • Biologicals: Rituximab, aldesleukin, natural killer cell infusion
    • Other: Laboratory biomarker analysis

    Active Comparator: High Risk

    Interventions

    • Drugs: Dexamethasone, vincristine sulfate, clofarabine, cyclophosphamide, etoposide, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, therapeutic hydrocortisone
    • Biologicals: Rituximab, aldesleukin, natural killer cell infusion
    • Procedure: Allogeneic hematopoietic stem cell transplantation
    • Other: Laboratory biomarker analysis

    Eligibility 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:
      • In first hematologic relapse, defined as the reappearance (in a patient who has previously achieved remission) of leukemia blasts in the bone marrow, OR
      • 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:
      • In first relapse, OR
      • Refractory to 1 or 2 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:
      • There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy.
      • 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.
      • 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 of 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.

    Study Design

    • Allocation: Non-Randomized
    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Parallel Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment
  2. About this clinical trial

    ALLR18 is a Phase II clinical trial for childhood precursor B-cell acute lymphoblastic leukemia and lymphoma that has come back after treatment the first time or did not respond to treatment.  ALL is a cancer that affects the white blood cells (the cells that fight infection and help protect the body against disease). Lymphomas are cancers that begin in the body’s lymphatic system.

    B-cell acute lymphoblastic leukemia and lymphoma that has returned or did not respond to treatment can be difficult to treat with chemotherapy alone. St. Jude researchers have learned new ways to kill cancerous cells with help from the body’s disease-fighting immune system and offer this Phase II clinical trial to find out how well the best options work to help prevent your child’s cancer from returning after treatment.

    View the ALLR18 Infographic.

    Purpose of this clinical trial

    The main goal is to find out how many participants treated on this study will have no signs or symptoms (remission) of leukemia or lymphoma and how many will still be in remission 3 years after taking part in this study.

    St. Jude researchers also want to find out how many participants taking part in this study will have negative MRD (minimal residual disease) after receiving very strong chemotherapy to put the leukemia or lymphoma in remission, compared to a previous St. Jude study. MRD is the major cause of disease coming back after treatment. It is the name given to small numbers of leukemic cells that remain in the blood or bone marrow during treatment or after treatment when a person’s leukemia is in remission.

    Treatment

    All participants will be given standard chemotherapy drugs along with:

    • A new chemotherapy drug known as clofarabine, which is shown to work well in patients with relapsed leukemia
    • Rituximab, a manmade form of an immune system protein, to find and kill leukemic cells without harming normal cells
    • Specially selected white blood cells called natural killer (NK) cells from the blood of a donor (usually a parent or close relative) to kill leukemic cells

    ALLR18 is the only such clinical trial that uses this three-way approach to increase cure rates for children with B-cell leukemia and lymphoma. Some participants in this clinical trial may receive a stem cell transplant, depending on the type of their disease and response to treatment.

    Eligibility overview

    • B-cell acute lymphoblastic leukemia or lymphoblastic lymphoma that has
      • Come back after treatment the first time
      • Did not respond to treatment the first time
    • Less than 22 years of age
    • Does not have HIV or hepatitis B infection
  3. ALLR18  Quick View
    Sponsor
     
    St. Jude Children's Research Hospital
    Collaborator Cookies for Kids’ Cancer
    ClinicalTrials.gov identifier NCT01700946
    Trial start date October 2012
    Estimated enrollment 40
    Study type Interventional
    Study phase Phase 2
    Conditions
    • Recurrent Childhood Acute B-lymphoblastic Leukemia
    • Recurrent Childhood B-lymphoblastic Lymphoma
    Ages Up to 21 years
    Principal investigator Sima Jeha, MD
    Study site St. Jude Children’s Research Hospital
    For a consultation or to discuss ALLR18 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Sima Jeha, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.