NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

June 7, 2022 updated by: St. Jude Children's Research Hospital

This is a phase II clinical trial using risk-adapted therapy. The treatment is acute lymphoblastic leukemia (ALL)-based therapy, using multi-agent regimens comprising of induction, consolidation, and continuation (maintenance) phases delivered over 24-30 months. Participants will be classified into 3 treatment stratums, based on bone marrow/peripheral blood lymphoma cells involvement at diagnosis and day 8 for T-lymphoblastic lymphoma and bone marrow/peripheral blood lymphoma cells involvement at diagnosis for B-lymphoblastic lymphoma.

The Primary Objective of this study is:

To improve the outcome of children with lymphoblastic lymphoma (LL) who have minimal disseminated disease (MDD) equal to or more than 1% at diagnosis by using MDD- and minimal residual disease (MRD)- based risk-adapted therapy.

The Secondary Objectives of this study are:

  • To estimate the event-free survival and overall survival of children with lymphoblastic lymphoma who are treated with MDD- or MRD-based risk- directed therapy.
  • To evaluate the prognostic value of levels of MDD at diagnosis and MRD on day 8 of remission induction.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

TREATMENT PLAN

Treatment will consist of 3 main phases: remission induction, consolidation [only for patients with any central nervous system (CNS) disease and/or testicular involvement], and continuation.

  • Induction (6-7 weeks).
  • Consolidation for participants with CNS involvement or those with testicular disease only (10 weeks).
  • Reintensification - Participants with residual disease any time after induction therapy may receive 1-2 cycles of re-intensification therapy and may proceed to allogeneic stem cell transplant if suitable donor is available.
  • Continuation Therapy (98-120 weeks).
  • Intrathecal Chemotherapy (days 1 and 15; if needed also on days 8 and 22)

TREATMENT SCHEME

T lymphoblastic lymphoma: bone marrow/peripheral blood (BM/PB) involvement (MDD/MRD): Diagnosis: less than 1%; Day 8: +/- (Stratum 1)

  • Induction

    • Single dose of Cyclophosphamide
    • Steroid: prednisone
  • Continuation: 98 weeks

T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: - (Stratum 2)

  • Induction

    • Fractionated Cyclophosphamide
    • Steroid: prednisone
  • Continuation : 98 weeks

T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: + (Stratum 3)

  • Induction

    • Fractionated Cyclophosphamide
    • Steroid: prednisone and dexamethasone
  • Continuation: 120 weeks

B lymphoblastic lymphoma: Stage I-III (Stratum 1)

  • Induction

    • Single dose of Cyclophosphamide
    • Steroid: prednisone
  • Continuation: 98 weeks

B lymphoblastic lymphoma: Stage IV or testicular (Stratum 2)

  • Induction

    • Fractionated Cyclophosphamide
    • Steroid: prednisone
  • Continuation: 98 weeks

Patients with CNS or testicular involvement will receive Consolidation therapy prior to continuation therapy and receive extended maintenance therapy (120 weeks).

Any patient with detectable disease (MRD, bone marrow or biopsy of residual mass) at the end of induction may be considered for reintensification and/or hematopoietic stem cell transplantation (HSCT).

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Diego, California, United States, 92123
        • Rady Children's Hospital San Diego
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of newly diagnosed lymphoblastic lymphoma (patients must have <25% tumor cells in bone marrow by morphology)
  2. Age ≤ 21 years
  3. Limited prior therapy, including systemic glucocorticoids for 1 week or less, 1 dose of vincristine, emergency radiation therapy to the mediastinum, and 1 dose of IT chemotherapy. Other circumstances must be cleared by PI or co-PI.
  4. Written, informed consent and assent following guidelines of the Institutional Review Board, National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP).

Exclusion Criteria:

  1. Participants with prior therapy, other than therapy specified in 3 above.
  2. Participants who are pregnant or lactating.
  3. Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

Patients will undergo treatment as described in the intervention section. Interventions include:

  • Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine
  • Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine
  • Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate
  • Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide
  • All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22.
Drug: Cyclophosphamide
Given IV.
Other Names:
  • Cytoxan®
Drug: Vincristine
Given intravenously (IV).
Other Names:
  • Oncovin®
  • Vincristine sulfate
Drug: Prednisone
Given orally (PO).
Other Names:
  • Prednisolone
Drug: Daunorubicin
Given IV.
Other Names:
  • Daunomycin
  • Cerubidine®
Drug: Mercaptopurine
Given PO.
Other Names:
  • 6-MP
  • Purinethol®
Drug: Doxorubicin
Given IV.
Other Names:
  • Adriamycin®
Drug: Etoposide
Given IV.
Other Names:
  • VP-16
  • Vepesid®
Drug: Clofarabine
Given IV.
Other Names:
  • Clofarex
  • CAFdA
  • Clolar^TM
  • Cl-F-Ara-A
  • 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
Drug: PEG-asparaginase
Given intramuscularly (IM) or IV.
Other Names:
  • Pegaspargase
  • Oncaspar®
Drug: Erwinia asparaginase
Given IM or IV if allergy occurs with the first or second PEG-asparaginase dose.
Other Names:
  • Erwinase®
Drug: Cytarabine
Given IV or IT.
Other Names:
  • Ara-C
  • Cytosar-U®
Drug: Thioguanine
Given PO.
Other Names:
  • Purine antimetabolite
Drug: Methotrexate
Given IV, IM or IT.
Other Names:
  • MTX
  • High-dose methotrexate (HD-MTX)
Drug: Dexamethasone
Given PO or IV.
Other Names:
  • Decadron®
Drug: Hydrocortisone
Given IT.
Other Names:
  • Cortef®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability of Event-free Survival (EFS)
Time Frame: Two years post therapy.

For EFS, relapse and second malignancies are considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. Kaplan-Meier estimates of the OS and EFS curves are computed, along with estimates of standard errors by Peto's method.

Please note the unit of measurement of probabilities are percentages.
Two years post therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Probability of Overall Survival (OS)
Time Frame: Two years post therapy.

For OS, only deaths are considered failures for OS. Kaplan-Meier estimates of the OS curves are computed along with estimates of standard errors by Peto's method.

Please note the unit of measurement of probabilities are percentages.
Two years post therapy.
Minimal Disseminated Disease (MDD)
Time Frame: At Diagnosis
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
At Diagnosis
Minimal Residual Disease (MRD)
Time Frame: Day 8
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
Day 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

National University, Singapore

Investigators

  • Principal Investigator: Hiroto Inaba, MD,PhD, St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2012

Primary Completion (Actual)

May 8, 2021

Study Completion (Actual)

May 31, 2022

Study Registration Dates

First Submitted

August 17, 2011

First Submitted That Met QC Criteria

October 11, 2011

First Posted (Estimate)

October 13, 2011

Study Record Updates

Last Update Posted (Actual)

June 28, 2022

Last Update Submitted That Met QC Criteria

June 7, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NHL16
  • NCI-2012-00496 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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