NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma

St. Jude Children's Research Hospital

Status and phase

Completed

Phase 2

Conditions

Lymphoblastic Lymphoma

Treatments

Drug: Daunorubicin

Drug: Clofarabine

Drug: Cyclophosphamide

Drug: Mercaptopurine

Drug: Methotrexate

Drug: PEG-asparaginase

Drug: Thioguanine

Drug: Vincristine

Drug: Doxorubicin

Drug: Hydrocortisone

Drug: Erwinia asparaginase

Drug: Dexamethasone

Drug: Prednisone

Drug: Etoposide

Drug: Cytarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT01451515

NHL16

NCI-2012-00496 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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).

Enrollment

23 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of newly diagnosed lymphoblastic lymphoma (patients must have <25% tumor cells in bone marrow by morphology)
Age ≤ 21 years
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.
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

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

23 participants in 1 patient group

Treatment

Experimental group

Description:

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.

Treatment:

Drug: Cytarabine

Drug: Etoposide

Drug: Dexamethasone

Drug: Prednisone

Drug: Hydrocortisone

Drug: Erwinia asparaginase

Drug: Doxorubicin

Drug: Vincristine

Drug: Thioguanine

Drug: Methotrexate

Drug: PEG-asparaginase