Velcade, Nipent, Rituxan (VNR) in Subjects With Relapsed Follicular, Marginal Zone, and Mantle Cell Lymphoma

NCT ID: NCT01460602

Last Updated: 2020-09-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-10-31

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)

Conditions

Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: establish MTD

Part 1 consists of dosing to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT).

Group Type: EXPERIMENTAL

MTD of Velcade, Nipent and Rituxan established in Part 1

Intervention Type: DRUG

One of the following dose levels will be chosen and used in Part 2:

1. (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

2. (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

3. (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

4. (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

Part 2: The MTD from Part 1

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.

Group Type: EXPERIMENTAL

MTD of Velcade, Nipent and Rituxan established in Part 1

Intervention Type: DRUG

One of the following dose levels will be chosen and used in Part 2:

1. (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

2. (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

3. (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

4. (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

Interventions

MTD of Velcade, Nipent and Rituxan established in Part 1

One of the following dose levels will be chosen and used in Part 2:

1. (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

2. (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

3. (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

4. (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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Voluntary written informed consent.

2. Male or female subject 18 years of age and older

3. Karnofsky Performance Status (KPS) score of 50%. ECOG Performance Status score greater than 2.

4. Histologically confirmed follicular Grade 1-3a, marginal zone or mantle cell NHL.

5. Relapsed or progressive disease after at least 1 prior chemotherapy requiring treatment.

6. Bi-dimensionally measurable disease with at least 1 lesion 2 cm in a single dimension

7. Hematologic, hepatic, and renal function parameters.

8. 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

9. Expected survival of 3 months

10. Accepted birth control methods during treatment and for 12 months after completion of treatment.

Exclusion Criteria

1. Follicular lymphoma Grade 3b

2. History of allergy to any of the study medications, their analogues, murine proteins, or excipients in the various formulations

3. Grade 2 peripheral neuropathy or clinical examination within 14 days before enrollment

4. Serum creatinine 2.5 mg/dL within 14 days before enrollment.

5. Absolute neutrophil count (ANC) < 1,000/L, platelet count < 70,000/L within 14 days before enrollment

6. Aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT/SGPT]) > 2 x the upper limit of normal (ULN), total bilirubin > 3 ULN

7. 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)

8. Cancer radiotherapy, biological therapy, or chemotherapy within 3 weeks prior to Study Day 1 (6 weeks if nitrosurea or mytomycin-C)

9. Prior lymphoma vaccine therapy within 12 months to Study Day 1

10. Prior antibody therapy for lymphoma (including radioimmunotherapy) within 6 months prior to Study Day 1

11. Autologous bone marrow or stem cell transplant within 6 months prior to Study Day 1

12. Known history of hepatitis or hepatic disease.

13. Presence of central nervous system (CNS) lymphoma

14. Known history of HIV infection or AIDS

15. Histologic transformation (Follicular or Marginal zone to diffuse large B cell lymphoma [DLBCL]

16. Presence of pleural or peritoneal effusion with positive cytology for lymphoma

17. Another primary malignancy requiring active treatment

18. 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

19. New York Heart Association Class III or IV (Appendix D) cardiac disease

20. Major surgery, other than diagnostic surgery, within 4 weeks prior to Study Day 1

21. Female subject who is pregnant or currently breast-feeding

22. Received other investigational drugs with 14 days before enrollment

23. Hypersensitivity to bortezomib, pentostatin, rituximab, boron or mannitol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Louisiana State University Health Sciences Center Shreveport

OTHER

Sponsor Role: lead

Responsible Party

Glenn Mills

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francesco Turturro, MD

Role: PRINCIPAL_INVESTIGATOR

LSUHSC-S

Locations

LSU - Shreveport Health Sciences Center, Feist-Weiller Cancer Center

Shreveport, Louisiana, United States

Countries

United States

Other Identifiers

X05266

Identifier Type: -

Identifier Source: org_study_id