Velcade, Nipent, Rituxan (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma
Primary Purpose
Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MTD of Velcade, Nipent and Rituxan established in Part 1
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma focused on measuring Lymphoma, Follicular, Marginal Zone, Mantle Cell, Velcade, bortezomib, Nipent, pentastatin, Rituxan, rituximab, Turturro, Shreveport
Eligibility Criteria
Inclusion Criteria:
- Voluntary written informed consent.
- Male or female subject 18 years of age and older
- Karnofsky Performance Status (KPS) score of 50%. ECOG Performance Status score greater than 2.
- Histologically confirmed follicular Grade 1-3a, marginal zone or mantle cell NHL.
- Relapsed or progressive disease after at least 1 prior chemotherapy requiring treatment.
- Bi-dimensionally measurable disease with at least 1 lesion 2 cm in a single dimension
- Hematologic, hepatic, and renal function parameters.
- Recovered fully from any significant toxicity associated with prior surgery, radiation treatments, chemotherapy, biological therapy, autologous bone marrow or stem cell transplant, or investigational drugs
- Expected survival of 3 months
- Accepted birth control methods during treatment and for 12 months after completion of treatment.
Exclusion Criteria:
- Follicular lymphoma Grade 3b
- History of allergy to any of the study medications, their analogues, murine proteins, or excipients in the various formulations
- Grade 2 peripheral neuropathy or clinical examination within 14 days before enrollment
- Serum creatinine 2.5 mg/dL within 14 days before enrollment.
- Absolute neutrophil count (ANC) < 1,000/L, platelet count < 70,000/L within 14 days before enrollment
- Aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT/SGPT]) > 2 x the upper limit of normal (ULN), total bilirubin > 3 ULN
- Rituxan refractory or refractory to anti-CD20 radioimmunotherapy (no response to prior Rituxan or prior Rituxan-containing regimen, or a response with a TTP of less than 6 months)
- Cancer radiotherapy, biological therapy, or chemotherapy within 3 weeks prior to Study Day 1 (6 weeks if nitrosurea or mytomycin-C)
- Prior lymphoma vaccine therapy within 12 months to Study Day 1
- Prior antibody therapy for lymphoma (including radioimmunotherapy) within 6 months prior to Study Day 1
- Autologous bone marrow or stem cell transplant within 6 months prior to Study Day 1
- Known history of hepatitis or hepatic disease.
- Presence of central nervous system (CNS) lymphoma
- Known history of HIV infection or AIDS
- Histologic transformation (Follicular or Marginal zone to diffuse large B cell lymphoma [DLBCL]
- Presence of pleural or peritoneal effusion with positive cytology for lymphoma
- Another primary malignancy requiring active treatment
- Serious non-malignant disease (e.g., congestive heart failure [CHF], hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions (including psychiatric), which would compromise protocol objectives n the opinion of the Investigator and/or Sponsor
- New York Heart Association Class III or IV (Appendix D) cardiac disease
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1
- Female subject who is pregnant or currently breast-feeding
- Received other investigational drugs with 14 days before enrollment
- Hypersensitivity to bortezomib, pentostatin, rituximab, boron or mannitol.
Sites / Locations
- LSU - Shreveport Health Sciences Center, Feist-Weiller Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part 1: establish MTD
Part 2: The MTD from Part 1
Arm Description
Part 1 consists of dosing to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT).
During the Phase 2 part of the study, approximately 24 additional subjects will be enrolled in order to obtain a total of 30 response-evaluable subjects treated at the maximum tolerated dose.
Outcomes
Primary Outcome Measures
CR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
ORR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
Secondary Outcome Measures
Maximum Tolerated Dose
Number of participants with adverse events as a measure of safety and tolerability
Rate of progression of disease
Summary data on time to progression of disease of study subjects
Full Information
NCT ID
NCT01460602
First Posted
June 10, 2010
Last Updated
August 28, 2020
Sponsor
Louisiana State University Health Sciences Center Shreveport
Collaborators
Millennium Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01460602
Brief Title
Velcade, Nipent, Rituxan (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma
Official Title
Phase 1/2 Study of VELCADE (Bortezomib), Nipent (Pentostatin), and Rituxan (Rituximab) (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Investigator has relocated to MD Anderson
Study Start Date
May 2010 (Actual)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Louisiana State University Health Sciences Center Shreveport
Collaborators
Millennium Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase 1/2 Study of VELCADE (bortezomib), Nipent (pentostatin), and Rituxan (rituximab) (VNR) in Subjects with Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma.
Detailed Description
Number of Subjects: During the Phase 1 part of the study as many as 15 subjects may be enrolled, based on the dose escalation scheme; the actual number of subjects enrolled will depend on the dose level at which the maximum tolerated dose (MTD) is established.
During the Phase 2 part of the study, approximately 15 subjects will be enrolled in order to obtain a total 30 response-evaluable subjects.
Study Objectives:
The primary objectives of this study are:
• Assess the CR and ORR following treatment with VELCADE (bortezomib), Nipent (pentostatin) and Rituxan (rituximab) (VNR) in subjects with follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) who have relapsed or been refractory after receiving at least 1 prior therapy.
The secondary objectives of this study are to:
Determine the MTD of VELCADE and Nipent in combination with Rituxan (VNR) in subjects with follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) who have relapsed or been refractory after receiving at least 1 prior therapy
Evaluate the safety and tolerability of VNR
Determine the time to response
Determine duration of response
Determine the time to progression (TTP)
Determine the progression free survival (PFS) rate
Determine the 1-year survival
Determine overall survival (OS)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma
Keywords
Lymphoma, Follicular, Marginal Zone, Mantle Cell, Velcade, bortezomib, Nipent, pentastatin, Rituxan, rituximab, Turturro, Shreveport
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: establish MTD
Arm Type
Experimental
Arm Description
Part 1 consists of dosing to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT).
Arm Title
Part 2: The MTD from Part 1
Arm Type
Experimental
Arm Description
During the Phase 2 part of the study, approximately 24 additional subjects will be enrolled in order to obtain a total of 30 response-evaluable subjects treated at the maximum tolerated dose.
Intervention Type
Drug
Intervention Name(s)
MTD of Velcade, Nipent and Rituxan established in Part 1
Intervention Description
One of the following dose levels will be chosen and used in Part 2:
(VAN1) VA= 1.3 mg/m2 IV Days 1, 4, 8, 11 N1= 2 mg/mg2 IV Days 1, 8 375 mg/m2 IV Day 1
(VAN2) VA= 1.3 mg/m2 IV Days 1, 4, 8, 11 N1= 4 mg/mg2 IV Days 1, 8 375 mg/m2 IV Day 1
(VBN1) VA= 1.5 mg/m2 IV Days 1, 4, 8, 11 N1= 2 mg/mg2 IV Days 1, 8 375 mg/m2 IV Day 1
(VBN2) VA= 1.5 mg/m2 IV Days 1, 4, 8, 11 N1= 4 mg/mg2 IV Days 1, 8 375 mg/m2 IV Day 1
Primary Outcome Measure Information:
Title
CR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
Description
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
Time Frame
up to 48 months
Title
ORR following treatment with VELCADE(bortezomib)/Nipent(pentostatin/Rituxan (rituximab)(VNR) in subjects with follicular lymphoma(FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL)relapsed or refractory after at least 1 prior therapy
Description
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
Time Frame
up to 48 months
Secondary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
Number of participants with adverse events as a measure of safety and tolerability
Time Frame
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
Title
Rate of progression of disease
Description
Summary data on time to progression of disease of study subjects
Time Frame
Study Days 1, 4, 8, 11 of 6 cycles (up to 3 weeks each) and Days 63/126, then Study Months 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Voluntary written informed consent.
Male or female subject 18 years of age and older
Karnofsky Performance Status (KPS) score of 50%. ECOG Performance Status score greater than 2.
Histologically confirmed follicular Grade 1-3a, marginal zone or mantle cell NHL.
Relapsed or progressive disease after at least 1 prior chemotherapy requiring treatment.
Bi-dimensionally measurable disease with at least 1 lesion 2 cm in a single dimension
Hematologic, hepatic, and renal function parameters.
Recovered fully from any significant toxicity associated with prior surgery, radiation treatments, chemotherapy, biological therapy, autologous bone marrow or stem cell transplant, or investigational drugs
Expected survival of 3 months
Accepted birth control methods during treatment and for 12 months after completion of treatment.
Exclusion Criteria:
Follicular lymphoma Grade 3b
History of allergy to any of the study medications, their analogues, murine proteins, or excipients in the various formulations
Grade 2 peripheral neuropathy or clinical examination within 14 days before enrollment
Serum creatinine 2.5 mg/dL within 14 days before enrollment.
Absolute neutrophil count (ANC) < 1,000/L, platelet count < 70,000/L within 14 days before enrollment
Aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT/SGPT]) > 2 x the upper limit of normal (ULN), total bilirubin > 3 ULN
Rituxan refractory or refractory to anti-CD20 radioimmunotherapy (no response to prior Rituxan or prior Rituxan-containing regimen, or a response with a TTP of less than 6 months)
Cancer radiotherapy, biological therapy, or chemotherapy within 3 weeks prior to Study Day 1 (6 weeks if nitrosurea or mytomycin-C)
Prior lymphoma vaccine therapy within 12 months to Study Day 1
Prior antibody therapy for lymphoma (including radioimmunotherapy) within 6 months prior to Study Day 1
Autologous bone marrow or stem cell transplant within 6 months prior to Study Day 1
Known history of hepatitis or hepatic disease.
Presence of central nervous system (CNS) lymphoma
Known history of HIV infection or AIDS
Histologic transformation (Follicular or Marginal zone to diffuse large B cell lymphoma [DLBCL]
Presence of pleural or peritoneal effusion with positive cytology for lymphoma
Another primary malignancy requiring active treatment
Serious non-malignant disease (e.g., congestive heart failure [CHF], hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions (including psychiatric), which would compromise protocol objectives n the opinion of the Investigator and/or Sponsor
New York Heart Association Class III or IV (Appendix D) cardiac disease
Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1
Female subject who is pregnant or currently breast-feeding
Received other investigational drugs with 14 days before enrollment
Hypersensitivity to bortezomib, pentostatin, rituximab, boron or mannitol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Turturro, MD
Organizational Affiliation
LSUHSC-S
Official's Role
Principal Investigator
Facility Information:
Facility Name
LSU - Shreveport Health Sciences Center, Feist-Weiller Cancer Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Velcade, Nipent, Rituxan (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma
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