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

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00151281
• Other study ID #: 047080073974
• Status: Completed
• Phase: Phase 2
• Start date: November 2004
• Est. completion date: April 7, 2011

Study information

• Verified date: June 2018
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: April 7, 2011
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

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
• 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)
• 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

Locations

Country	Name	City	State
United States	Weill Medical College of Cornell University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival and Progression Free Survival	measured by overall Response Rate (ORR), which includes Complete response and partial response.	38 months
Secondary	Asses the Toxicity Profiles	Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.	38 months
Secondary	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
Secondary	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