Clinical Trial: Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

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

Official Title: A Phase I/II Trial of CHOEP Chemotherapy Plus Lenalidomide as Front Line Therapy for Patients With Stage II, III and IV Peripheral T-Cell Non-Hodgkin Lymphoma

Brief Summary: This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, 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. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of lenalidomide in combination with standard induction therapy (CHOEP- cyclophosphamide, doxorubicin [doxorubicin hydrochloride], etoposide, vincristine [vincristine sulfate] and prednisone) in patients with newly diagnosed stage II, III and IV peripheral T-cell lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma (anaplastic lymphoma receptor tyrosine kinase [ALK] negative) (ALK positive if International Prognostic Index [IPI] 3, 4, or 5), angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma or hepatosplenic gamma delta T-cell lymphoma.

II. To establish the maximum tolerated dose of lenalidomide in combination with CHOEP chemotherapy. (Phase I) III. To assess the efficacy (complete response rate) of this combination. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (complete response [CR] + partial response [PR]) of the combination of lenalidomide and CHOEP chemotherapy.

II. To evaluate the safety and tolerability of the regimen. III. To assess the 2 year progression free survival (PFS) and overall survival (OS) using this regimen.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide, followed by a phase II study.

Patients receive cyclophosphamide intravenously (IV), doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone orally (PO) on days 1-5 and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxici
Sponsor: University of Nebraska

Current Primary Outcome:

  • Maximum tolerated dose of lenalidomide and CHOEP, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: 21 days ]
  • Incidence of toxicity graded according to Common Toxicity Criteria (CTC) (Phase I) [ Time Frame: Up to 1 year ]
    Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
  • Complete response rate (Phase II) [ Time Frame: Up to the completion of course 6 (18 weeks) ]
    A success is defined to be an objective status of CR after completion of 6 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A 95% confidence interval for the true overall CR rate will be calculated according to the method of Duffy and Santner.
  • Overall response rate [ Time Frame: Up to the completion of course 6 (18 weeks) ]
    The ORR will be estimated by the total number of patients who achieve a PR or CR at the end of six cycles of treatment divided by the total number of evaluable patients. Exact b

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Incidence of toxicity graded according to CTC (Phase II) [ Time Frame: Up to 1 year ]
      The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
    • Progression-free survival [ Time Frame: Time from registration to progression or death due to any cause, assessed up to 2 years ]
      The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest.
    • Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 1 year ]
      The distribution of overall survival will be estimated using the method of Kaplan-Meier.


    Original Secondary Outcome: Same as current

    Information By: University of Nebraska

    Dates:
    Date Received: September 24, 2015
    Date Started: October 2015
    Date Completion:
    Last Updated: October 30, 2016
    Last Verified: October 2016