Phase II Study of RT-PEPC in Relapsed Mantle Cell Lymphoma

Study Overview
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Brief Summary
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Primary Objective: Evaluate the clinical activity of the RT-PEPC combination regimen (rituximab, thalidomide, and prednisone, etoposide, procarbazine, cyclophosphamide) in patients with relapsed mantle cell lymphoma. Specifically, response rate (RR) and time to disease progression (TTP) will be assessed. Secondary Objectives: Assess the toxicity profiles of RT-PEPC treatment in patients with relapsed mantle cell lymphoma. Prospectively characterize the angiogenic profile of patients with mantle cell lymphoma during treatment with RT-PEPC. The dynamics of the angiogenic profile will be correlated with clinical response to RT-PEPC therapy. Assess the quality of life of patients receiving RT-PEPC treatment

Official Title
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Phase II Trial of Anti-Angiogenic Therapy With RT-PEPC in Patients With Relapsed Mantle Cell Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: PEPC
* Drug: Thalidomide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profiles: CD5(+),CD23(-), CD19(+) or CD20(+), cyclin D1(+), and CD10(-) Patient has persistent / recurrent disease after standard chemotherapy Patient has not received either standard or investigational drugs within the last 3 weeks Available frozen tumor tissue obtained since completion of last prior therapy (rebiopsy if needed) Patient has measurable disease as defined by a tumor mass > 1.5 cm in one dimension Age > 18 years Absolute granulocyte count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN Patient has KPS > 50% Patient agrees to use birth control if of reproductive potential Exclusion Criteria: Known central nervous system (CNS) involvement by lymphoma Known HIV disease Known peripheral neuropathy > grade 2 Patient is pregnant or nursing Patient has had major surgery within the last 3 weeks Patient is receiving other investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Treatment Arm<br> | Drug: PEPC<br>* Induction phase (month 1-3) • PEPC daily (prednisone 20 mg/day, cyclophosphamide 50 mg/day, etoposide 50 mg/day, and procarbazine 50 mg/day) until expected drop in neutrophil count (ANC < 3000), unless due to disease. After ANC returns to above 2,000/ul, PEPC resumes at alternate day or fractionated weekly basis. Maintenance phase (month 4-12) • PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase (post-month 12 until disease progression) • PEPC QOD or fractionated weekly basis<br>* Other names: Prednisone, Cyclophosphamide, Etoposide, Procarbazine;Drug: Thalidomide<br>* Induction phase (month 1-3) • Daily thalidomide at 50 mg/day for the first 8 weeks, then dose escalated as tolerated to a maximum of 100 mg/day. Maintenance phase (month 4-12) • Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase (post-month 12 until disease progression) • Daily low dose thalidomide (50-100mg/d)<br>Drug: Rituximab<br>* Induction phase (month 1-3) • Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase (month 4-12) • Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase (post-month 12 until disease progression) • Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival and Progression Free Survival | measured by overall Response Rate (ORR), which includes Complete response and partial response. | 38 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asses the Toxicity Profiles | Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. | 38 months | 
| Dynamic Levels of Plasma VEGF | Stromal angiogenesis was assessed using blood vascular and perivascular markers, including VEGFR-1, VEGFR-2, CD34, and a-SMA, as well as lymphatic vascular markers ofVEGFR-3, podoplanin, and Lyve-1. | 38 months | 
| The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment | QoL assessments were obtained with version 3 of the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. The FACT-G is comprised of four subscales: physical well-being (7-items, score range 0-28), social/family well-being (7-items, score range 0-28), emotional well-being (6-items, score range 0-24), and functional well-being (7-items, score range 0-28). Users of the FACT-G are able to generate an overall score and four subscale scores with ranges and distributions that are sample-specific. All questions in the FACT-G use a 5-point rating scale (0 = Not at all to 4 = Very much) A higher number indicates a better Quality of Life, and has a possible range of 0-108 points. ANOVA was used to compare the difference in the means of total score among the different time points (baseline, every 2M until 6M, and every 6M until PD). The mean of the total FACT-G scores at baseline and mean of total score at all timepoints (using ANOVA) are reported below. | baseline, every 2 months until Month 6, and every 6 months until disease progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed mantle cell lymphoma