Clinical trial NCT01451515: NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma
Official title: NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoblastic Lymphoma
Keywords: Lymphoblastic lymphoma
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: National University of Singapore
First posted: 2011-10-13
Enrollment: 23
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility 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.

Primary outcomes:
measure: Probability of Event-free Survival (EFS)
timeFrame: Two years post therapy.
Secondary outcomes:
measure: Probability of Overall Survival (OS)
timeFrame: Two years post therapy.
measure: Minimal Disseminated Disease (MDD)
timeFrame: At Diagnosis
measure: Minimal Residual Disease (MRD)
timeFrame: Day 8
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Hiroto Inaba, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: