NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

Lymphoblastic Lymphoma Clinical Trial

Official title:

NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01451515
• Other study ID #: NHL16
• Secondary ID: NCI-2012-00496
• Status: Completed
• Phase: Phase 2
• Start date: May 25, 2012
• Est. completion date: May 31, 2022

Study information

• Verified date: June 2022
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: May 31, 2022
• Est. primary completion date: May 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoblastic Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Prednisone
Given orally (PO).
• Vincristine
Given intravenously (IV).
• Daunorubicin
Given IV.
• PEG-asparaginase
Given intramuscularly (IM) or IV.
• Erwinia asparaginase
Given IM or IV if allergy occurs with the first or second PEG-asparaginase dose.
• Doxorubicin
Given IV.
• Cyclophosphamide
Given IV.
• Cytarabine
Given IV or IT.
• Thioguanine
Given PO.
• Clofarabine
Given IV.
• Methotrexate
Given IV, IM or IT.
• Mercaptopurine
Given PO.
• Dexamethasone
Given PO or IV.
• Hydrocortisone
Given IT.
• Etoposide
Given IV.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Rady Children's Hospital San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	National University, Singapore

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Probability of Event-free Survival (EFS)	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	Probability of Overall Survival (OS)	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.
Secondary	Minimal Disseminated Disease (MDD)	Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)	At Diagnosis
Secondary	Minimal Residual Disease (MRD)	Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)	Day 8

External Links

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