Clinical Trial: Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Intensified Methotrexate, Nelarabine (Compound 506U78) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-cell Acute Lymphoblastic Leukemia (AL

Brief Summary: This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group [CCG]-1961).

II. To determine the relative safety and efficacy of high dose methotrexate (5 g/m^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance.

III. To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival.

SECONDARY OBJECTIVES:

I. To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation.

OUTLINE:

INDUCTION THERAPY: (weeks 1-5) Patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV and daunorubicin hydrochloride IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) or IV over 1-2 hours on day 4, 5, OR 6; and methotrexate (MTX) IT on days 8 and 29*. Patients with Down syndrome (DS) also receive leucovorin calcium PO at 48 and 60 hours after each MTX dose (DS patients excluded as of 09/29/10).

After completion of induction therapy, patients undergo risk assessment. Patients with M1 marrow and minimal residual diseas
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Efficacy of combination chemotherapy with vs without nelarabine [ Time Frame: Up to 10 years ]
    "Intent-to-treat" analyses (i.e. based on the regimen to which patients are initially randomized) will be the primary approach used to assess treatment efficacy.
  • Efficacy of high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs escalating-dose methotrexate (without leucovorin calcium rescue) and pegaspargase [ Time Frame: Up to 10 years ]
    Analyses will be performed regularly to assess the possibility of an interaction effect (using a Cox regression likelihood ratio test) which will assess the four individual treatment regimens in the 2 x 2 design to see if a non-proportional hazards effect occurs for the combinations of the two main effect factors. Since the comparison of the methotrexate regimens utilizes a selection type analysis, no futility testing will be used for that comparison.
  • Event-free survival (EFS) after initial remission [ Time Frame: At 4 years ]
    This outcome can be modeled reasonably well by a linear decreasing hazard rate with no appreciable risk of failure after completion of year 4. EFS events include any type of relapse, death in remission or second malignant neoplasm. "Intent-to-treat" analyses (i.e. based on the regimen to which patients are initially randomized) will be the primary approach used to assess treatment efficacy.
  • Incidence of toxicities of combination chemotherapy with vs without nelarabine as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ]
  • Inciden

    Original Primary Outcome:

    • Event-free survival after initial remission
    • Toxicity of nelarabine
    • Safety and efficacy of combination chemotherapy with vs without nelarabine
    • Safety and efficacy of high-dose methotrexate with leucovorin calcium rescue and mercaptopurine vs escalating-dose methotrexate without leucovorin calcium rescue and pegaspargase


    Current Secondary Outcome:

    • Incidence of CNS relapse [ Time Frame: Up to 10 years ]
      Examined for various treatment regimen comparisons, and in the subset of patients who will not receive XRT CNS prophylaxis.
    • Overall survival [ Time Frame: Up to 10 years ]


    Original Secondary Outcome:

    • CNS relapse
    • Overall survival


    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: December 4, 2006
    Date Started: January 2007
    Date Completion:
    Last Updated: May 11, 2017
    Last Verified: May 2017