NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
National University, Singapore
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01451515
First received: August 17, 2011
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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 determine event-free and overall survival
  • Investigate the relationship between Day 8 MRD and MDD results and EFS

Condition Intervention Phase
Lymphoblastic Lymphoma
Drug: prednisone, vincristine, daunorubicin, PEG-asparaginase, methotrexate, hydrocortisone, cytarabine (IT-MH)A treatment, cyclophosphamide, cytarabine, thioguanine
Drug: PEG- asparaginase, High-Dose Methotrexate (HD-MTX) and Mercaptopurine
Drug: Dexamethasone, Doxorubicin; Vincristine; Mercaptopurine; PEG- Asparaginase, Cyclophosphamide, and Cytarabine
Drug: dexamethasone, cytarabine, etoposide, pegaspargase, clofarabine, cyclophosphamide
Drug: Intrathecal chemotherapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival (EFS). [ Time Frame: Two years post therapy. ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curve estimate.


Secondary Outcome Measures:
  • Overall survival (OS). [ Time Frame: Two years post therapy. ] [ Designated as safety issue: No ]
    Kaplan-Meier survival curve estimate.

  • Percentage of lymphoblastic cells in bone marrow at diagnosis (MDD) and at day 8 of therapy (MRD). [ Time Frame: Two years post day 8. ] [ Designated as safety issue: No ]
    Cox regression modeling of EFS with MRD and MDD as explanatory variables.


Estimated Enrollment: 72
Study Start Date: May 2012
Estimated Study Completion Date: October 2024
Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Patients will undergo treatment as described in the intervention section.
Drug: prednisone, vincristine, daunorubicin, PEG-asparaginase, methotrexate, hydrocortisone, cytarabine (IT-MH)A treatment, cyclophosphamide, cytarabine, thioguanine
Remission induction treatment will begin with prednisone, vincristine, daunorubicin, PEG-asparaginase and IT-MHA treatment, followed by cyclophosphamide plus cytarabine plus thioguanine. Prednisone is replaced by dexamethasone on day 15 in patients with T-lymphoblastic lymphoma having MDD ≥1% at diagnosis and MRD positive on day 8. For patients with heterozygous or homozygous TPMT genotype, 6-mercaptopurine is used instead of thioguanine.
Other Name: Remission induction
Drug: PEG- asparaginase, High-Dose Methotrexate (HD-MTX) and Mercaptopurine
When absolute neutrophil count (ANC) of >300/mm3, white blood count (WBC) of greater than or equal to 1000/mm3, and platelet count of greater than or equal to 50 × 109/L are reached, consolidation treatment will be started, consisting of PEG-asparaginase (every alternate week for 5 doses), HD-MTX (every alternate week for 4 doses, not concurrent with PEG-asparaginase), daily mercaptopurine, and IT chemotherapy (on the same days as HD-MTX).
Other Name: Consolidation
Drug: Dexamethasone, Doxorubicin; Vincristine; Mercaptopurine; PEG- Asparaginase, Cyclophosphamide, and Cytarabine
Postremission continuation treatment will be initiated after the completion of remission induction (consolidation for patients with CNS and/or testicular disease) if ANC is greater than or equal to 300/mm3, WBC is greater than or equal to 1000/mm3, and platelet count is greater than or equal to 50 × 109/L as well as no evidence of grade 3 or 4 mucositis.
Other Name: Continuation
Drug: dexamethasone, cytarabine, etoposide, pegaspargase, clofarabine, cyclophosphamide
Patients with detectable disease, bone marrow morphology, or MRD of bone marrow or peripheral blood after induction receive dexamethasone PO or IV, cytarabine IV, etoposide IV, IT-MHA, and pegaspargase IM. Patients achieving suboptimal response also receive clofarabine IV, etoposide IV, cyclophosphamide IV, and dexamethasone. Patients are offered HSCT.
Other Name: Reintensification
Drug: Intrathecal chemotherapy
All patients receive IT-MHA comprising methotrexate intrathecally (IT), therapeutic hydrocortisone IT, and cytarabine IT injection on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22.
Other Name: IT-MHA

  Show Detailed Description

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451515

Contacts
Contact: Hiroto Inaba, MD,PhD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Hiroto Inaba, MD,Ph.D    866-278-5833    info@stjude.org   
Principal Investigator: Hiroto Inaba, MD,Ph.D         
Sponsors and Collaborators
St. Jude Children's Research Hospital
National University, Singapore
Investigators
Principal Investigator: Hiroto Inaba, MD,PhD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01451515     History of Changes
Other Study ID Numbers: NHL16
Study First Received: August 17, 2011
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Lymphoblastic lymphoma

Additional relevant MeSH terms:
Lymphoma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Leukemia
6-Mercaptopurine
Cytarabine
Methotrexate
Thioguanine
Clofarabine
Cyclophosphamide
Etoposide phosphate
Pegaspargase
Asparaginase
Daunorubicin
Dexamethasone
Doxorubicin
Etoposide
Prednisone
Vincristine
BB 1101
Dexamethasone acetate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate

ClinicalTrials.gov processed this record on August 19, 2014