Trial Outcomes & Findings for Phase II Study of RT-PEPC in Relapsed Mantle Cell Lymphoma (NCT NCT00151281)
NCT ID: NCT00151281
Last Updated: 2018-06-28
Results Overview
measured by overall Response Rate (ORR), which includes Complete response and partial response.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
38 months
Results posted on
2018-06-28
Participant Flow
Participant milestones
| Measure |
RT-PEPC Drug Therapy
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 Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
RT-PEPC Drug Therapy
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 Study
Not evaluable
|
3
|
Baseline Characteristics
Phase II Study of RT-PEPC in Relapsed Mantle Cell Lymphoma
Baseline characteristics by cohort
| Measure |
RT-PEPC Drug Therapy
n=25 Participants
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
|
|---|---|
|
Age, Continuous
|
68 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 38 monthsPopulation: Twenty-five patients were enrolled, and 22 of those patients were assessable for response (3 patients were enrolled but received no therapy)
measured by overall Response Rate (ORR), which includes Complete response and partial response.
Outcome measures
| Measure |
Study Treatment Arm
n=22 Participants
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
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|---|---|
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Overall Survival and Progression Free Survival
|
73 percentage of patients
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SECONDARY outcome
Timeframe: 38 monthsPopulation: patients treated with study drug
Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
Outcome measures
| Measure |
Study Treatment Arm
n=22 Participants
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
|
|---|---|
|
Asses the Toxicity Profiles
Grade 3 or 4 neutropenia
|
14 Participants
|
|
Asses the Toxicity Profiles
Anemia
|
1 Participants
|
|
Asses the Toxicity Profiles
Thrombocytopenia
|
4 Participants
|
|
Asses the Toxicity Profiles
Fatigue
|
22 Participants
|
|
Asses the Toxicity Profiles
Constipation
|
14 Participants
|
|
Asses the Toxicity Profiles
Cough
|
14 Participants
|
|
Asses the Toxicity Profiles
Nausea
|
13 Participants
|
|
Asses the Toxicity Profiles
Neuropathy
|
13 Participants
|
|
Asses the Toxicity Profiles
Dyspnea
|
11 Participants
|
|
Asses the Toxicity Profiles
Rash
|
10 Participants
|
SECONDARY outcome
Timeframe: 38 monthsPopulation: subjects with evaluable VEGF level at baseline
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.
Outcome measures
| Measure |
Study Treatment Arm
n=20 Participants
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
|
|---|---|
|
Dynamic Levels of Plasma VEGF
|
109.5 pg/mL
Interval 7.0 to 319.0
|
SECONDARY outcome
Timeframe: baseline, every 2 months until Month 6, and every 6 months until disease progressionQoL 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.
Outcome measures
| Measure |
Study Treatment Arm
n=22 Participants
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
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|---|---|
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The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment
Mean FACT-G Score at baseline
|
83.3 FACT-G score
Interval 64.5 to 102.1
|
|
The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment
Mean Total FACT-G Score between all time points
|
89.4 FACT-G score
Interval 83.9 to 94.9
|
Adverse Events
Study Treatment Arm
Serious events: 1 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Study Treatment Arm
n=22 participants at risk
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
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
pneumocystis carinii pneumonia
|
4.5%
1/22 • Number of events 1
|
Other adverse events
| Measure |
Study Treatment Arm
n=22 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
90.9%
20/22
|
|
Blood and lymphatic system disorders
Anemia
|
63.6%
14/22
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
63.6%
14/22
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia/ Upper Respiratory Illness
|
40.9%
9/22
|
|
General disorders
Fever
|
31.8%
7/22
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
13.6%
3/22
|
|
General disorders
Opportunistic infection
|
9.1%
2/22
|
|
General disorders
Fatigue
|
100.0%
22/22
|
|
Gastrointestinal disorders
Constipation
|
63.6%
14/22
|
|
General disorders
Cough
|
63.6%
14/22
|
|
General disorders
Nausea
|
59.1%
13/22
|
|
Nervous system disorders
Neuropathy
|
59.1%
13/22
|
|
General disorders
Dyspnea
|
50.0%
11/22
|
|
Skin and subcutaneous tissue disorders
Rash
|
45.5%
10/22
|
|
General disorders
Dizziness
|
45.5%
10/22
|
|
General disorders
Abdominal pain
|
36.4%
8/22
|
|
Immune system disorders
Alopecia
|
36.4%
8/22
|
|
General disorders
Vomiting
|
27.3%
6/22
|
|
Blood and lymphatic system disorders
Deep Vein Thrombosis/ pulmonary embolism
|
9.1%
2/22
|
|
Cardiac disorders
Transient ischemic attack
|
4.5%
1/22
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place