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

NCT01460602 | Withdrawn Phase 1

• 1 other identifier: X05266
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Follicular Lymphoma; Marginal Zone Lymphoma; Mantle Cell Lymphoma

Keywords

Lymphoma; Follicular; Marginal Zone; Mantle Cell; Velcade; bortezomib; Nipent; pentastatin; Rituxan; rituximab; Turturro; Shreveport

Outcome Measures

Primary Outcomes (2)

• 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

  up to 48 months

• 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

  up to 48 months

Secondary Outcomes (2)

• Maximum Tolerated Dose

  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

• Rate of progression of disease

  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

Study Arms (2)

Part 1: establish MTD

EXPERIMENTAL

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

Drug: MTD of Velcade, Nipent and Rituxan established in Part 1

Part 2: The MTD from Part 1

EXPERIMENTAL

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.

Drug: MTD of Velcade, Nipent and Rituxan established in Part 1

Interventions

MTD of Velcade, Nipent and Rituxan established in Part 1 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 1: establish MTD; Part 2: The MTD from Part 1

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[DLBCL\]

Sponsors & Collaborators

• Louisiana State University Health Sciences Center Shreveport: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

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

Shreveport, Louisiana, 71103, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Lymphoma

Interventions

Pentostatin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Francesco Turturro, MD

  LSUHSC-S

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: October 27, 2011
• Study Start: May 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: September 1, 2020

Record last verified: 2020-07

Locations

US (1)