Clinical Trial: Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-L

Brief Summary: This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) in patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LLy) who are randomized to a modified augmented Berlin-Frankfurt-Münster (ABFM) backbone versus bortezomib plus the modified ABFM backbone.

SECONDARY OBJECTIVES:

I. To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy based on the results of UKALL 2003, which includes a dexamethasone-based induction, additional doses of pegaspargase (PEG-ASP) during induction and delayed intensification (DI), and dexamethasone pulses during maintenance therapy.

II. To determine if prophylactic (presymptomatic) cranial irradiation (CRT) can be safely and effectively eliminated in the 85-90% of T-ALL patients classified as standard or intermediate risk.

III. To determine the proportion of end of consolidation (EOC) minimal residual disease (MRD) >= 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS between the patients who become MRD negative after the three HR BFM blocks and continue on chemotherapy with those who continue to have detectable MRD and are eligible for other treatment strategies, including hematopoietic stem cell transplant (HSCT). Similarly, to compare the EFS between very high risk (induction failure) T-LLy patients treated with HR BFM intensification blocks who have partial or complete response (PR or CR) with those who do not respond (NR).

TERTIARY OBJECTIVES:

Interim monitoring for efficacy and futility will be performed. The study will also be monitored for futility using the method of Freidlin and Korn.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Cumulative incidence rates [ Time Frame: Up to 10 years ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
  • EFS [ Time Frame: Up to 10 years ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
  • EFS between very high risk (VHR) T-ALL patients treated with HR BFM intensification blocks who become MRD negative and those who remain MRD positive at the end of HR Block 3 [ Time Frame: Up to 10 years ]
    The proportion of VHR T-ALL patients with EOC MRD >= 0.1% who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy, will be estimated. EFS for these patients (who continue on chemotherapy) will be compared with those who continue to have detectable MRD and who may receive other treatment options including hematopoietic stem cell transplant. Comparison will be descriptive.
  • EFS between VHR T-LLy patients treated with HR BFM intensification blocks who have partial remission or complete remission with those who do not respond [ Time Frame: Up to 10 years ]
    Comparison will be descriptive.
  • Incidence of toxicity associated with modified standard therapy, including dexamethasone and additional pegaspargase as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ]
    Safety data will also be compared between the two arms.


Original Secondary Outcome:

  • EFS [ Time Frame: Up to 10 years ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
  • Cumulative incidence rates [ Time Frame: Up to 10 years ]
    Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
  • Incidence of toxicity associated with modified standard therapy, including dexamethasone and additional pegaspargase as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 10 years ]
    Safety data will also be compared between the two arms.
  • EFS between VHR T-ALL patients treated with HR BFM intensification blocks who become MRD negative and those who remain MRD positive at the end of HR Block 3 [ Time Frame: Up to 10 years ]
    The proportion of VHR T-ALL patients with EOC MRD >= 0.1% who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy, will be estimated. EFS for these patients (who continue on chemotherapy) will be compared with those who continue to have detectable MRD and who may receive other treatment options including hematopoietic stem cell transplant. Comparison will be descriptive.
  • EFS between VHR T-LLy patients treated with HR BFM intensification blocks who have partial remission (PR) or complete remission (CR) with those who do not respond (NR) [ Time Frame: Up to 10 years ]
    Comparison will be descriptive.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 9, 2014
Date Started: September 2014
Date Completion:
Last Updated: May 19, 2017
Last Verified: May 2017