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

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

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:

1. Assess the toxicity profiles of RT-PEPC treatment in patients with relapsed mantle cell lymphoma.
2. 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.
3. Assess the quality of life of patients receiving RT-PEPC treatment

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: PEPC; Drug: Thalidomide; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Treatment Arm

Drug: PEPC; 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; Other Names: Prednisone, Cyclophosphamide, Etoposide, Procarbazine; Drug: Thalidomide; 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); Drug: Rituximab; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University

Publications and helpful links

General Publications

• Ruan J, Martin P, Coleman M, Furman RR, Cheung K, Faye A, Elstrom R, Lachs M, Hajjar KA, Leonard JP. Durable responses with the metronomic rituximab and thalidomide plus prednisone, etoposide, procarbazine, and cyclophosphamide regimen in elderly patients with recurrent mantle cell lymphoma. Cancer. 2010 Jun 1;116(11):2655-64. doi: 10.1002/cncr.25055.

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): April 7, 2011

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 7, 2005
• First Posted (Estimate): September 8, 2005

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: relapsed mantle cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cyclophosphamide; Etoposide; Thalidomide; Rituximab; Prednisone; Procarbazine
• Other Study ID Numbers: 047080073974