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

NCT01700946 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: ALLR18NCI-2012-00587
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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.

Conditions

Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood B-Lymphoblastic Lymphoma

Keywords

leukemia; lymphoma; Non-Hodgkins

Outcome Measures

Primary Outcomes (2)

• 3-year Overall Survival Rate of Patients With Relapsed ALL

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

  3 years of follow-up since the on-study date

• 3-year Event-free Survival Rates in Patients With Relapsed ALL

  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.

  3 years of follow-up since the on-study date

Secondary Outcomes (3)

• Proportion of Participants With Positive Minimal Residual Disease

  At end of induction (approximately 3 months)

• Mean of CD20 Expression Levels

  Baseline and at the end of Block I (approximately 5 weeks after the on-study date)

• Median CD20 Expression Levels

  Baseline and at the end of Block I (approximately 5 weeks after the on-study date)

Study Arms (2)

Standard Risk

ACTIVE COMPARATOR

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; 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; Device: CliniMACS

High Risk

ACTIVE COMPARATOR

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; Drug: vincristine sulfate; Biological: rituximab; Drug: clofarabine; Drug: cyclophosphamide; Drug: etoposide; Biological: aldesleukin; Drug: pegaspargase; Drug: methotrexate; Drug: mercaptopurine; Drug: cytarabine; Drug: mitoxantrone; Biological: natural killer cell infusion; Other: laboratory biomarker analysis; Drug: therapeutic hydrocortisone; Procedure: allogeneic hematopoietic stem cell transplantation; Device: CliniMACS

Interventions

dexamethasone DRUG

given intravenously or orally

Also known as: Decadron(R)

High Risk; Standard Risk

vincristine sulfate DRUG

given intravenously

Also known as: Oncovin(R)

High Risk; Standard Risk

rituximab BIOLOGICAL

given intravenously

Also known as: Rituxan(R)

High Risk; Standard Risk

clofarabine DRUG

given intravenously

Also known as: Clolar(TM), clofarex

High Risk; Standard Risk

cyclophosphamide DRUG

given intravenously

Also known as: Cytoxan(R)

High Risk; Standard Risk

etoposide DRUG

given intravenously

Also known as: VP-16, Vepesid(R)

High Risk; Standard Risk

aldesleukin BIOLOGICAL

given subcutaneously

Also known as: IL-2, interleukin-2, Proleukin (R)

High Risk; Standard Risk

pegaspargase DRUG

given intravenously

Also known as: PEG-ASP, Peg-L-asparaginase, PEG-asparaginase, Oncaspar(R)

High Risk; Standard Risk

methotrexate DRUG

given intrathecally or intravenously

Also known as: MTX, HDMTX

High Risk; Standard Risk

mercaptopurine DRUG

given orally

Also known as: 6-MP, Purinethol(R)

High Risk; Standard Risk

cytarabine DRUG

given intrathecally or intravenously

Also known as: Ara-C, Cytosar-U(R)

High Risk; Standard Risk

mitoxantrone DRUG

given intravenously

Also known as: Novantrone(R)

High Risk; Standard Risk

teniposide DRUG

given intravenously

Also known as: VM-26, Vumon(R)

Standard Risk

vinblastine DRUG

given intravenously

Also known as: Velban(R)

Standard Risk

natural killer cell infusion BIOLOGICAL

undergo allogeneic natural killer cell infusion

Also known as: NK cell infusion

High Risk; Standard Risk

laboratory biomarker analysis OTHER

correlative studies

High Risk; Standard Risk

therapeutic hydrocortisone DRUG

given intrathecally

Also known as: Cortef

High Risk; Standard Risk

allogeneic hematopoietic stem cell transplantation PROCEDURE

undergo allogeneic HSCT

Also known as: HSCT

High Risk

CliniMACS DEVICE

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.

Also known as: Cell Selection System

High Risk; Standard Risk

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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 peripheral blood, OR
• 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:
• In first relapse, OR
• 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:
• 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.

You may not qualify if:

• 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.
• Donor is at least 18 years of age.
• Donor is a family member.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Cookies for Kids' Cancer: collaborator
• Assisi Foundation: collaborator

Study Sites (3)

Rady Children's Hospital and Health Center

San Diego, California, 92123, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia; Lymphoma

Interventions

Dexamethasone; Vincristine; Rituximab; Clofarabine; Cyclophosphamide; Etoposide; aldesleukin; Interleukin-2; pegaspargase; Methotrexate; Mercaptopurine; Cytarabine; Mitoxantrone; Teniposide; Vinblastine; Hydrocortisone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Adenine Nucleotides; Purine Nucleotides; Purines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors; Aminopterin; Pterins; Pteridines; Sulfhydryl Compounds; Sulfur Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Anthraquinones; Anthrones; Anthracenes; Quinones; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Sima Jeha, MD
• Organization: St. Jude Children's Research Hospital

sima.jeha@stjude.org

(901) 595-3901

Study Officials

• Sima Jeha, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2012
• First Posted: October 4, 2012
• Study Start: April 15, 2013
• Primary Completion: July 24, 2021
• Study Completion: July 24, 2021
• Last Updated: September 28, 2022
• Results First Posted: September 28, 2022

Record last verified: 2022-09

Locations

US (3)