Combination Chemotherapy and Nelarabine in Treating Patients With T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Overview

This phase II trial studies the side effects and how well combination chemotherapy and nelarabine work in treating patients with T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine, mercaptopurine, prednisone, pegaspargase, nelarabine, and venetoclax work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Full Title of Study: “Phase II Study of Hyper-CVAD Plus Nelarabine in Previously Untreated T-ALL and Lymphoblastic Lymphoma”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 31, 2024

Detailed Description

PRIMARY OBJECTIVES: I. To determine the complete remission (CR) rate and progression-free survival following treatment with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with nelarabine in previously untreated patients with T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma. II. To determine the safety and overall survival of previously untreated patients with T-cell ALL and T-cell lymphoblastic lymphoma. III. To determine the safety and efficacy of adding pegaspargase to the regimen. IV. To determine the safety and efficacy of adding venetoclax to the regimen. OUTLINE: COURSES 1, 3, 5, and 7 (hyper-CVAD): Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on day 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV over 15-30 minutes on days 4 and 11, and dexamethasone IV or orally (PO) once daily (QD) on days 1-4 and 11-14. COURSES 2, 4, 6, and 8 (methotrexate/cytarabine): Patients receive methotrexate IV over 24 hours on day 1 and cytarabine IV over 2 hours BID on days 2 and 3. Patients also receive venetoclax PO QD on days 1-14 of each course. Courses of hyper-CVAD and methotrexate/cytarabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive nelarabine IV over 2 hours once daily (QD) for 5 days and pegaspargase IV over 2 hours on day 5 after completion of course 4 and after the completion of course 5 in the absence of disease progression or unacceptable toxicity. MAINTENANCE COURSES 1-5, 8-17, and 20-30 (mercaptopurine, vincristine, methotrexate, and prednisone [POMP]): Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO once weekly, vincristine sulfate IV on day 1, prednisone PO QD on days 1-5, and venetoclax PO QD on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. INTENSIFICATION COURSES 6 and 7: Patients receive nelarabine IV QD over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5. Patients also receive venetoclax PO QD on days 1-14. Courses repeat every 21-35 days in the absence of disease progression or unacceptable toxicity. INTENSIFICATION COURSES 18 and 19: Patients receive methotrexate IV over 2 hours on day 1, pegaspargase IV over 2 hours on day 2, and venetoclax PO QD on days 1-14 in the absence of disease progression or unacceptable toxicity. POMP maintenance therapy continues for 30 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months.

Interventions

  • Drug: Cyclophosphamide
    • Given IV
  • Drug: Cytarabine
    • Given IV
  • Drug: Dexamethasone
    • Given IV or PO
  • Drug: Doxorubicin Hydrochloride
    • Given IV
  • Drug: Mercaptopurine
    • Given PO
  • Drug: Methotrexate
    • Given IV and PO
  • Drug: Nelarabine
    • Given IV
  • Drug: Pegaspargase
    • Given IV
  • Drug: Prednisone
    • Given PO
  • Drug: Venetoclax
    • Given PO
  • Drug: Vincristine Sulfate
    • Given IV

Arms, Groups and Cohorts

  • Experimental: Treatment (nelarabine and combination chemotherapy)
    • See Detailed Description

Clinical Trial Outcome Measures

Primary Measures

  • Complete remission rate
    • Time Frame: 3 years
    • The sample size will provide an estimate of relapse rate at 3 years with a 95% confidence interval of width +/- 10%.
  • Duration of remission
    • Time Frame: Up to 9 years
    • Duration of remission will be evaluated.
  • Progression-free survival
    • Time Frame: 3 years
    • Progression-free survival will be estimated.
  • Overall survival
    • Time Frame: 3 years
    • Overall survival will be estimated.

Participating in This Clinical Trial

Inclusion Criteria

  • Previously untreated T cell ALL including T cell lymphoblastic lymphoma; failure to one induction course of chemotherapy are eligible; patients in CR after =< 2 courses are also eligible – Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3 – Serum bilirubin less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 5.0 mg/dL is acceptable – Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) less than or equal to 4 x upper limit of normal (ULN) – Serum creatinine less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 2.5 mg/dL is acceptable Exclusion Criteria:

  • Pregnant or nursing women

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • M.D. Anderson Cancer Center
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Farhad Ravandi-Kashani, Principal Investigator, M.D. Anderson Cancer Center
  • Overall Contact(s)
    • Farhad Ravandi-Kashani, MD, 713-745-0394

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.