Non-Hodgkin's Lymphoma
Conditions
Keywords
relapsed mantle cell lymphoma
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
Interventions
DRUGPEPC
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
DRUGThalidomide
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)
DRUGRituximab
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
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival and Progression Free Survival | 38 months | measured by overall Response Rate (ORR), which includes Complete response and partial response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Asses the Toxicity Profiles | 38 months | Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not evaluable | 3 |
Baseline characteristics
| Characteristic | RT-PEPC Drug Therapy |
|---|---|
| Age, Continuous | 68 years |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 1 / 22 |
Outcome results
Primary
Overall Survival and Progression Free Survival
measured by overall Response Rate (ORR), which includes Complete response and partial response.
Time frame: 38 months
Population: Twenty-five patients were enrolled, and 22 of those patients were assessable for response (3 patients were enrolled but received no therapy)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Treatment Arm | Overall Survival and Progression Free Survival | 73 percentage of patients |
Secondary
Asses the Toxicity Profiles
Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
Time frame: 38 months
Population: patients treated with study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Treatment Arm | Asses the Toxicity Profiles | Nausea | 13 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Neuropathy | 13 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Dyspnea | 11 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Grade 3 or 4 neutropenia | 14 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Anemia | 1 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Thrombocytopenia | 4 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Fatigue | 22 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Constipation | 14 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Cough | 14 Participants |
| Study Treatment Arm | Asses the Toxicity Profiles | Rash | 10 Participants |
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.
Time frame: 38 months
Population: subjects with evaluable VEGF level at baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study Treatment Arm | Dynamic Levels of Plasma VEGF | 109.5 pg/mL |
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.
Time frame: baseline, every 2 months until Month 6, and every 6 months until disease progression
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Study Treatment Arm | The Quality of Life (QoL) of Patients Receiving RT-PEPC Treatment | Mean FACT-G Score at baseline | 83.3 FACT-G score |
| Study Treatment Arm | 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 |