A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma

NCT00290706 | Terminated Phase 1 Results DMC

• 3 other identifiers: NU 04H4VEL-03-082STU00007425
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with bortezomib may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with gemcitabine and to see how well they work in treating patients with relapsed or refractory B-cell or T-cell non-Hodgkin's lymphoma.

Conditions

Lymphoma

Keywords

recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 3 follicular lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome

Outcome Measures

Primary Outcomes (1)

• Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment.

  Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission \[CR\] and Partial Remission \[PR\]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where: CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=\> 50% decrease in SPD of the six largest dominant nodes or nodal masses

  At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8

Secondary Outcomes (3)

• Time to Treatment Failure and Duration of Response

  At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

• Overall Survival

  Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

• Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy

  During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment

Study Arms (1)

Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds

EXPERIMENTAL

Gemcitabine dose of 800 mg/m2 over 30 minutes followed by Bortezomib IVP given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.

Drug: bortezomib; Drug: gemcitabine hydrochloride

Interventions

bortezomib DRUG

Bortezomib 1.6mg/m2 on days 1 and 15 of each cycle, given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.

Also known as: Velcade®, PS-341

Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds

gemcitabine hydrochloride DRUG

Gemcitabine dose of 800 mg/m2 over 30 minutes on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.

Also known as: Gemzar®

Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of B- or T-cell non-Hodgkin's lymphoma (NHL) * Intermediate histology B-cell NHL, including any of the following: * Diffuse large B-cell lymphoma * Transformed large cell lymphoma * Any T-cell NHL histology * Cutaneous T-cell lymphoma (CTCL) or mycosis fungoides (MF) allowed * Relapsed or refractory disease, defined as disease progressed after prior complete remission (CR), partial remission (PR), or stable disease (SD) to last therapy OR failure to achieve CR, PR, or SD after completion of last therapy * Must have received 1-3 prior therapeutic regimens * Cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) AND cyclophosphamide, vincristine, and prednisone (CVP) OR CHOP with rituximab (CHOP-R) AND CVP with rituximab (CVP-R) is considered 1 regimen * Monoclonal antibody (e.g., rituximab) given as maintenance therapy is considered 1 regimen * Salvage chemotherapy followed by an autologous stem cell transplant is considered 1 regimen * No more than 7 prior therapeutic regimens for patients with CTCL or MF * No mantle cell lymphoma PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 3 months * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * At least 50,000/mm\^3 if documented bone marrow involvement * Hemoglobin ≥ 8.0 g/dL * AST and ALT ≤ 3 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * Bilirubin ≤ 2 times ULN * Creatinine ≤ 2.0 mg/dL * No known history of HIV infection * No other active infection * No uncontrolled hypertension * No peripheral neuropathy ≥ grade 2 within the past 2 weeks * No myocardial infarction within the past 6 months * No New York Heart Association class III or IV heart failure * No uncontrolled angina * No severe uncontrolled ventricular arrhythmias * No acute ischemia or active conduction system abnormalities by ECG * No hypersensitivity to bortezomib, boron, or mannitol * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier-method contraception * No serious medical or psychiatric illness that would preclude study participation PRIOR CONCURRENT THERAPY: * Prior autologous and/or allogeneic stem cell transplantation allowed * More than 3 weeks since prior chemotherapy, radiotherapy, or immunotherapy * More than 3 weeks since prior systemic biologic anticancer therapy * More than 3 weeks since prior systemic corticosteroids (e.g., oral prednisone \> 10 mg per day) * More than 2 weeks since prior investigational drug * No prior bortezomib or gemcitabine hydrochloride * No other concurrent systemic cytotoxic chemotherapy or investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Northwestern University: lead
• Eli Lilly and Company: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, 60611, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

Bortezomib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Lymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Limitations and Caveats

The study was terminated before the accrual goal was met as it was determined that the study lacked efficacy. Most patients did not reach 3 cycles of treatment in order to be evaluable for response.

Results Point of Contact

• Title: Leo Gordon
• Organization: Northwestern University

l-gordon@northwestern.edu

312-695-4520

Study Officials

• Leo Gordon, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2006
• First Posted: February 13, 2006
• Study Start: April 7, 2006
• Primary Completion: February 11, 2011
• Study Completion: September 5, 2012
• Last Updated: May 28, 2019
• Results First Posted: May 28, 2019

Record last verified: 2019-05

Locations

US (3)