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.
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 toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Undergo autologous stem cell transplant
Given IV
Given IV
Given IV
Correlative studies
Given PO
Undergo peripheral blood stem cell transplant
Given PO
Given IV
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Stanford Cancer Institute
Palo Alto, California, United States
University of Colorado Cancer Center, Anschutz Cancer Pavilion
Aurora, Colorado, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP
MTD is 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) within the first cycle of study treatment.
Time frame: 21 days
Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I)
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.
Time frame: Up to 6 cycles of treatment (approximately 5 months)
Complete Response Rate (Phase II)
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.
Time frame: Up to the completion of course 6 (18 weeks)
Overall Response Rate
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 binomial 95% confidence intervals for the true ORR will be calculated.
Time frame: Up to the completion of course 6 (18 weeks)
Number of Participants With Adverse Events Graded According to CTC (Phase II)
The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence of maximum tolerated dose level of the Intent to treat (ITT) group of subjects is summarized. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group.
Time frame: Up to 1 year
Overall Survival
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to death due to any cause, assessed up to 1 year
Progression-free Survival
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.
Time frame: Time from registration to progression or death due to any cause, assessed up to 2 years
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