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

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00151281
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arm: 1
• Duration (Months): 77.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: PEPC; Drug: Thalidomide; Drug: Rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Anti-Angiogenic Therapy With RT-PEPC in Patients With Relapsed Mantle Cell Lymphoma
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Apr 7, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall Survival and Progression Free Survival [38 months]

   measured by overall Response Rate (ORR), which includes Complete response and partial response.

Secondary Outcome Measures

1. Asses the Toxicity Profiles [38 months]

   Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.

2. Dynamic Levels of Plasma VEGF [38 months]

   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.

3. The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment [baseline, every 2 months until Month 6, and every 6 months until disease progression]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Medical College of Cornell University	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University

Investigators

• Principal Investigator: John P Leonard, MD, Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT00151281
• Other Study ID Numbers: 047080073974
• First Posted: Sep 8, 2005
• Last Update Posted: Jun 28, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Weill Medical College of Cornell University: relapsed mantle cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Thalidomide; Prednisone; Cyclophosphamide; Rituximab; Etoposide; Procarbazine

Study Results

Participant Flow

Arm/Group Title	RT-PEPC Drug Therapy
Arm/Group Description	PEPC Induction phase 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 PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase PEPC QOD or fractionated weekly basis Thalidomide Induction phase 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 Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase Daily low dose thalidomide (50-100mg/d) Rituximab Induction phase Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Period Title: Overall Study
STARTED	25
COMPLETED	22
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	RT-PEPC Drug Therapy
Arm/Group Description	PEPC Induction phase 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 PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase PEPC QOD or fractionated weekly basis Thalidomide Induction phase 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 Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase Daily low dose thalidomide (50-100mg/d) Rituximab Induction phase Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Overall Participants	25
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68
Sex: Female, Male (Count of Participants)
Female	6 24%
Male	19 76%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Twenty-five patients were enrolled, and 22 of those patients were assessable for response (3 patients were enrolled but received no therapy)

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Rituximab, Thalidomide, Prednisone, Etoposide, Procarbazine, Cyclophosphamide: 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. Daily thalidomide at 50 mg/day for the first 8 weeks, then dose escalated as tolerated to a maximum of 100 mg/day. Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase (month 4-12) Daily low dose thalidomide (50-100 mg/d) PEPC QOD or fractionated weekly basis. Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase (post-month 12 until disease progression) Daily low dose thalidomide (50-100mg/d) PEPC QOD or fractionated weekly basis Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Measure Participants	22
Number [percentage of patients]	73

2. Secondary Outcome

Title	Asses the Toxicity Profiles
Description	Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

patients treated with study drug

Arm/Group Title	RT-PEPC Drug Therapy
Arm/Group Description	PEPC Induction phase 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 PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase PEPC QOD or fractionated weekly basis Thalidomide Induction phase 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 Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase Daily low dose thalidomide (50-100mg/d) Rituximab Induction phase Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Measure Participants	22
Grade 3 or 4 neutropenia	14 56%
Anemia	1 4%
Thrombocytopenia	4 16%
Fatigue	22 88%
Constipation	14 56%
Cough	14 56%
Nausea	13 52%
Neuropathy	13 52%
Dyspnea	11 44%
Rash	10 40%

3. Secondary Outcome

Title	Dynamic Levels of Plasma VEGF
Description	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.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

subjects with evaluable VEGF level at baseline

Arm/Group Title	RT-PEPC Drug Therapy
Arm/Group Description	PEPC Induction phase 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 PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase PEPC QOD or fractionated weekly basis Thalidomide Induction phase 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 Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase Daily low dose thalidomide (50-100mg/d) Rituximab Induction phase Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Measure Participants	20
Median (Full Range) [pg/mL]	109.5

4. Secondary Outcome

Title	The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment
Description	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.
Time Frame	baseline, every 2 months until Month 6, and every 6 months until disease progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RT-PEPC Drug Therapy
Arm/Group Description	PEPC Induction phase 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 PEPC QOD or fractionated weekly basis. Post-Month 12 Maintenance phase PEPC QOD or fractionated weekly basis Thalidomide Induction phase 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 Daily low dose thalidomide (50-100 mg/d) Post-Month 12 Maintenance phase Daily low dose thalidomide (50-100mg/d) Rituximab Induction phase Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
Measure Participants	22
Mean FACT-G Score at baseline	83.3
Mean Total FACT-G Score between all time points	89.4

Adverse Events

Arm/Group Title	Study Treatment Arm
Arm/Group Description	Rituximab, Thalidomide, Prednisone, Etoposide, Procarbazine, Cyclophosphamide: 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. Daily thalidomide at 50 mg/day for the first 8 weeks, then dose escalated as tolerated to a maximum of 100 mg/day. Rituximab weekly x 4 (375 mg/m2/week) starting at week 1. Maintenance phase (month 4-12) Daily low dose thalidomide (50-100 mg/d) PEPC QOD or fractionated weekly basis. Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months. Post-Month 12 Maintenance phase (post-month 12 until disease progression) Daily low dose thalidomide (50-100mg/d) PEPC QOD or fractionated weekly basis Rituximab (375 mg/m2/week) weekly x 4 administered every 4 months
All Cause Mortality
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
pneumocystis carinii pneumonia	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Study Treatment Arm
	Affected / at Risk (%)	# Events
Total	22/22 (100%)
Blood and lymphatic system disorders
Neutropenia	20/22 (90.9%)
Anemia	14/22 (63.6%)
Thrombocytopenia	14/22 (63.6%)
Febrile Neutropenia	3/22 (13.6%)
Deep Vein Thrombosis/ pulmonary embolism	2/22 (9.1%)
Cardiac disorders
Transient ischemic attack	1/22 (4.5%)
Gastrointestinal disorders
Constipation	14/22 (63.6%)
General disorders
Fever	7/22 (31.8%)
Opportunistic infection	2/22 (9.1%)
Fatigue	22/22 (100%)
Cough	14/22 (63.6%)
Nausea	13/22 (59.1%)
Dyspnea	11/22 (50%)
Dizziness	10/22 (45.5%)
Abdominal pain	8/22 (36.4%)
Vomiting	6/22 (27.3%)
Immune system disorders
Alopecia	8/22 (36.4%)
Nervous system disorders
Neuropathy	13/22 (59.1%)
Respiratory, thoracic and mediastinal disorders
Pneumonia/ Upper Respiratory Illness	9/22 (40.9%)
Skin and subcutaneous tissue disorders
Rash	10/22 (45.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.