Back to resultsBortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)
Primary Purpose
Mantle Cell Lymphoma
Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rituximab
bortezomib
Cladribine
Sponsored by
About this trial
This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring mantle cell lymphoma, lymphoma
Eligibility Criteria
Inclusion Criteria:
- Females that are postmenopausal for at least 1 year before the screening visit, surgically sterilized or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose.
- Male subjects must agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Patients with newly diagnosed and relapsed mantle cell lymphoma.
- ECOG performance status grade 3 or higher.
Exclusion Criteria:
- Patient has a platelet count of <50x10 9/L within 14 days before enrollment if not related to disease.
- Patient has an absolute neutrophil count less than 100 within 14 days before enrollment if not related to disease.
- Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
- Patient has > 1.5 x ULN total bilirubin.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class II or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Female subject is pregnant or breast-feeding.
- Patient has received other investigational drugs within 14 days before enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
Sites / Locations
- Penn State Cancer Institute
- Penn State Milton S. Hershey Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase I
Phase II
Arm Description
The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of cladribine in the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Rituximab 375 mg/m2 on day 5,12, 19, 26 for 1st cycle, then day 5 of cladribine for next 5 cycles and then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days 1-5 for 6 cycles. Bortezomib 1.6 mg/m2 sub Q days 12,19,26 for 3 cycle, then every 2 weeks maintenance dose until toxicity or progression.
The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms. Rituximab 375 mg/m2 on day 5,12,19,26 for 1st cycles, then day 5 montly for next 5 cycles, then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days for 6 cycles (dose determined from phase I). Bortezomib 1.6 mg/m2 weekly on day 12,19,26 for 3 cycles then every 2 weeks as maintenance dose until toxicity or progression.
Outcomes
Primary Outcome Measures
Primary Outcome Dose Limiting Tolerability
Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .
Secondary Outcome Measures
Secondary Outcome objective response rates
Estimate objective response rates of the VCR regimen in B cell malignancies where response to therapy is assessed per the revised Cheson criteria (2007) and the overall survival of patients treated with this combination for the Phase 2 portion of the study.
Full Information
NCT ID
NCT01439750
First Posted
August 16, 2011
Last Updated
August 4, 2017
Sponsor
Milton S. Hershey Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT01439750
Brief Title
Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)
Official Title
Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma: A Phase I/II Study (PSHCI 10-011)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
May 2012 (Actual)
Primary Completion Date
August 2018 (Anticipated)
Study Completion Date
August 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Milton S. Hershey Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a phase I/II trial of bortezomib, cladribine, and rituximab in newly diagnosed and relapsed mantle cell lymphoma (MCL). The phase I component has three dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2) and is designed as a traditional dose-escalation study in which cohorts of 3 patients are evaluated for the incidence of dose-liming toxicity (DLT) at each dose level. Once the maximum tolerated dose (MTD) is determined, a phase II component with 2 arms will begin. One arm will enroll newly diagnosed MCL patients and one arm will enroll relapsed MCL patients. Each arm is a single-stage, fixed sample size study and will be accrued and analyzed separately. The phase I and II data will also be analyzed separately.
Detailed Description
The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Three patients are enrolled on a dose level. If 0 out of 3 patients have DLT, then the next set of 3 patients are enrolled at the next highest dose level. If ≥2 out of 3 patients have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be enrolled at the next lowest dose level if only 3 were treated previously at that level. If 1 out of 3 patients have DLT, then the next set of 3 patients will be treated at the same dose level. If ≤1 out of 6 patients treated at that dose level have DLT, then the next set of patients will be treated at the next higher dose level. If ≥2 out of 6 patients treated at that dose level have DLT, then the MTD will have been exceeded and dose escalation will cease. Three additional patients will be treated at the next lowest dose level if only 3 were treated previously at that level. This phase I study will use 3 dose levels of cladribine (3 mg/m2, 4 mg/m2, and 5 mg/m2), with 3 mg/m2 being the starting dose level. DLTs will be assessed at the completion of the first 2 cycles of cladribine and rituximab.
Phase II Design: The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms.
Due to difficulties with enrollment, this trial will not move into the intended Phase II of the proposed Phase I/II study. This study will only be Phase I.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
mantle cell lymphoma, lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase I
Arm Type
Experimental
Arm Description
The phase I portion of the study is a standard dose-escalation schemed designed to determine the maximum tolerated dose (MTD) of cladribine in the combination of bortezomib, cladribine, and rituximab therapy. The MTD is defined as the dose level in which ≤1 out of 6 patients have dose-limiting toxicity (DLT). Rituximab 375 mg/m2 on day 5,12, 19, 26 for 1st cycle, then day 5 of cladribine for next 5 cycles and then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days 1-5 for 6 cycles. Bortezomib 1.6 mg/m2 sub Q days 12,19,26 for 3 cycle, then every 2 weeks maintenance dose until toxicity or progression.
Arm Title
Phase II
Arm Type
Experimental
Arm Description
The phase II portion of the study is a two-arm, single-stage design with no interim analysis. One arm will accrue newly diagnosed patients, and one arm will accrue relapsed patients. In each arm, the progression-free survival rate at 2 years will be used as the primary endpoint for determining whether the treatment is sufficiently active in each arm. No comparisons will be made between the arms. Rituximab 375 mg/m2 on day 5,12,19,26 for 1st cycles, then day 5 montly for next 5 cycles, then every 2 months maintenance dose. Cladribine 3-5 mg/m2 days for 6 cycles (dose determined from phase I). Bortezomib 1.6 mg/m2 weekly on day 12,19,26 for 3 cycles then every 2 weeks as maintenance dose until toxicity or progression.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxam
Intervention Description
375 mg/m2 on day 5, 12, 19, 26 of Cycle1; and day 5 of Cycles 2-6; then every 2 months as maintenenace dose
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
VELCADE
Intervention Description
1.6 mg/m2 day 12, 19, 26 for 3 cycles (28 days). Then beginning with Cycle 4, 1.6/mg/m2 every two weeks (Days 5 and 19; maintenance every other week until toxicity or proression of disease).
Intervention Type
Drug
Intervention Name(s)
Cladribine
Other Intervention Name(s)
Litak, Movectro
Intervention Description
Phase I will use 3 dose levels Level 1: caldribine (2-CdA) 3mg/m2 days 1-5; Level 2 caldribine 4mg/m2 days 1-5; Level 3: cladribine 5mg/m2 days 1-5
Primary Outcome Measure Information:
Title
Primary Outcome Dose Limiting Tolerability
Description
Dose Limiting Tolerability as measured by CTCAEv.4 criteria and to evaluate progression free survival in patients treated with VCR in the Phase 1 portion .
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Secondary Outcome objective response rates
Description
Estimate objective response rates of the VCR regimen in B cell malignancies where response to therapy is assessed per the revised Cheson criteria (2007) and the overall survival of patients treated with this combination for the Phase 2 portion of the study.
Time Frame
7 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Females that are postmenopausal for at least 1 year before the screening visit, surgically sterilized or if they are of childbearing potential agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose.
Male subjects must agree to practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
Patients with newly diagnosed and relapsed mantle cell lymphoma.
ECOG performance status grade 3 or higher.
Exclusion Criteria:
Patient has a platelet count of <50x10 9/L within 14 days before enrollment if not related to disease.
Patient has an absolute neutrophil count less than 100 within 14 days before enrollment if not related to disease.
Patient has a calculated or measured creatinine clearance of <20 mL/minute within 14 days before enrollment.
Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
Patient has > 1.5 x ULN total bilirubin.
Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class II or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
Patient has hypersensitivity to bortezomib, boron or mannitol.
Female subject is pregnant or breast-feeding.
Patient has received other investigational drugs within 14 days before enrollment.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey J Pu, MD PhD
Organizational Affiliation
Milton S. Hershey Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State Cancer Institute
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Penn State Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
May share data
Learn more about this trial
Bortezomib (VELCADE), Cladribine and Rituximab (VCR) in Mantle Cell Lymphoma (PSHCI 10-011)
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