Untreated Mantle Cell Lymphoma
Conditions
Brief summary
Primary Objective 1\. To evaluate the safety profile of Bevacizumab (Bevacizumab™)- Rituximab (Rituxan®)-CHOP (RA-CHOP) in patients with newly diagnosed mantle cell lymphoma (MCL). Secondary Objectives 1. To evaluate the response rate and time to disease progression of the RA-CHOP regimen in patients with newly diagnosed MCL. 2. To prospectively characterize the angiogenic profiles of MCL patients during RA-CHOP treatment.
Detailed description
Bevacizumab administered at 15 mg/kg on day 1 of each of 6 cycles Rituximab administered 375 mg/m2 on day 3 of each of 6 cycles (with usual premedications) Standard CHOP chemotherapy administered on day 3 every 21 days (full dose) for 6 cycles of treatment Once completed six cycles of therapy (\ 18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.
Interventions
DRUGBevacizumab
15 mg/kg on day 1 of each of 6 cycles
DRUGRituximab
Rituximab will be administered prior to CHOP on day 3 of every cycle for a total of 6 cycles. The dose to be administered is: Rituximab: 375 mg/m2
DRUGCHOP
Standard CHOP chemotherapy will be administered at full dose every 21 days for a total of 6 cycles. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 3 Doxorubicin: 50 mg/m2 IV on day 3 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 3 Prednisone: 100 mg PO days 3 - 7
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 profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-) * Patient has not received any prior anti-cancer therapy for lymphoma * Laboratory parameters (unless considered by investigator to be due to lymphoma): Absolute neutrophil count \> 1000 cells/mm3 Platelet count \> 50,000 cells/mm3 Hemoglobin \> 7 gm/dL Creatinine \< 2.0 x ULN Total bilirubin \< 2.0 x ULN * Patient has at least one tumor mass \> 1.5 cm in one dimension * Available tumor tissue for correlative studies (rebiopsy to be performed if needed) * Patient is \> 18 years old * Patient has KPS \> 50% * Patient has signed IRB-approved informed consent * Patient agrees to use birth control for duration of study
Exclusion criteria
* Known central nervous system (CNS) involvement by lymphoma * Known hepatitis infection * Known HIV positivity * Known history of renal disease with proteinuria; urine protein:creatinine ratio ³1.0 at screening * Uncontrolled hypertension: blood pressure of \>150/100 mmHg at screening * Unstable angina * History of myocardial infarction within 6 months * History of stroke within 6 months * Clinically significant peripheral vascular disease * New York Heart Association (NYHA) Grade II or greater congestive heart failure * Patient has ejection fraction \< 50% * Patient is taking coumadin, or has known history of thrombosis within last 6 months * Evidence of bleeding diathesis or coagulopathy * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1 * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 * Serious, non-healing wound, ulcer, or bone fracture * Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. * Patient is pregnant or nursing * Patient is receiving other investigational drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Toxicity | 38 months | Number of patients with reversible myelosuppression (Primary toxicity was reversible myelosuppression) Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 38 Months (min 33 months, max 62 months) | Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999) |
| Progression-Free Survival | 3 years | The percentage of patients who have not progressed at the three year time point. The 3-year PFS rate was estimated based on the Kaplan-Meier analysis. |
| Overall Survival | 3 years | The percentage of patients who have survived at the three year time point. The 3-year OS rate was estimated based on the Kaplan-Meier analysis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Treatment Arm Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles
Bevacizumab: 15 mg/kg on day 1 of each of 6 cycles | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Study Treatment Arm |
|---|---|
| Age, Continuous | 60 years |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 1 / 11 |
Outcome results
Primary
Number of Participants With Toxicity
Number of patients with reversible myelosuppression (Primary toxicity was reversible myelosuppression) Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
Time frame: 38 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Treatment Arm | Number of Participants With Toxicity | 8 participants |
Secondary
Overall Response Rate
Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999)
Time frame: 38 Months (min 33 months, max 62 months)
Population: Evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Treatment Arm | Overall Response Rate | 82 percentage of participants |
Secondary
Overall Survival
The percentage of patients who have survived at the three year time point. The 3-year OS rate was estimated based on the Kaplan-Meier analysis.
Time frame: 3 years
Population: Evaluable Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Treatment Arm | Overall Survival | 82 percentage of patients |
Secondary
Progression-Free Survival
The percentage of patients who have not progressed at the three year time point. The 3-year PFS rate was estimated based on the Kaplan-Meier analysis.
Time frame: 3 years
Population: Evaluable patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Treatment Arm | Progression-Free Survival | 23 percentage of patients |