Pilot Study of Bortezomib, Bendamustine and Rituximab on Non-Hodgkin's Lymphoma

NCT00547534 | Completed Phase 2 Results DMC

• 1 other identifier: ULYM07054
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate how non-Hodgkin's lymphoma that has not responded to, or that has returned after standard treatment, responds to bortezomib, rituximab and bendamustine, and also to see what effects this drug combination have on this cancer.

Conditions

Non-Hodgkin's Lymphoma

Keywords

Bortezomib; Bendamustine; Rituximab; Relapsed; Refractory; Mantle Cell; Indolent

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression Free Survival at 2 Years

  To determine the progression-free survival following treatment with the BVR combination in patients with relapsed or refractory indolent and mantle cell non-Hodgkin lymphoma.

  Two years

Secondary Outcomes (2)

• Toxicity of Drug Combination in the Subjects

  Two years

• Overall Response Rate (ORR)

  Two years

Study Arms (1)

Lymphoma Subjects receiving protocol therapy

EXPERIMENTAL

Subjects that met all eligibility criteria and were treated with Bendamustine, Rituxan and Bortezomib.

Drug: bortezomib; Drug: bendamustine; Drug: rituximab

Interventions

bortezomib DRUG

1.3 mg/m\^2 on days 1, 4, 8, 11

Also known as: Velcade

Lymphoma Subjects receiving protocol therapy

bendamustine DRUG

90 mg/m\^2 days 1 and 4

Also known as: Treanda

Lymphoma Subjects receiving protocol therapy

rituximab DRUG

375 mg/m\^2 day 1

Also known as: Rituxan

Lymphoma Subjects receiving protocol therapy

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent before performance of any study-specific procedure not part of routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is either post-menopausal or surgically sterilized or willing to use acceptable method of birth control for duration of study.
• Male subject agrees to use acceptable method for contraception for duration of study.
• Histologically-confirmed indolent or mantle cell lymphoma, utilizing the World Health Organization (WHO) classification. The biopsy must fulfill one of the following criteria:
• Follicular lymphoma, grades 1-3
• Marginal zone lymphoma
• Small lymphocytic lymphoma (circulating lymphocyte count must be \< 5,000)
• Lymphoplasmacytic lymphoma
• Mantle cell lymphoma \[confirmed by cyclin D1+ or FISH for t(11;14)\]
• Age ≥ 18 years
• Must have received at least one prior chemotherapy regimen for lymphoma. Patients treated only with antibody therapy or only with radiation therapy are not eligible.
• Zubrod performance status ≤ 3
• Patients must have measurable disease or an indication to receive additional therapy

You may not qualify if:

• Patient has platelet count of ≤75,000/mm\^3 within 14 days before enrollment.
• Patient has absolute neutrophil count of \< 1,000/mm\^3 within 14 days before enrollment.
• Patient has calculated or measured creatinine clearance of \<30 mL/minute within 14 days before enrollment.
• Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to boron or mannitol
• Female subject is pregnant or breast-feeding. Confirmation subject is not pregnant must be established by negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received chemotherapy or antibody therapy within 28 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patient has received other investigational drugs with 14 days before enrollment
• 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.
• Prior exposure to bendamustine
• Prior exposure to bortezomib if Time to Progression (TTP) after bortezomib containing regimen was \< 6 months. If TTP after bortezomib containing regimen was \> 6 months, then patient is allowed to enroll on the study.
• Patient has concomitant active malignancy requiring therapy
• Patient is known to be HIV positive (test result not required for enrollment).

Sponsors & Collaborators

• University of Rochester: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Cephalon: collaborator

Study Sites (3)

Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cornell Wiell Medical College

New York, New York, 10021, United States

Location

University of Rochester Medical Center (James P. Wilmot Cancer Center)

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. doi: 10.1182/blood-2010-11-314708. Epub 2011 Jan 14.

  PMID: 21239695 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Recurrence

Interventions

Bortezomib; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butyrates; Acids, Acyclic; Carboxylic Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

19 patients received a full 6 cycles of therapy. All patients received at least one cycle of therapy, 25 patients received at least 4 cycles. Reasons for early termination included progressive disease and toxicity

Results Point of Contact

• Title: Dr. Jonathan Friedberg
• Organization: University of Rochester Medical Center

Jonathan_Friedberg@urmc.rochester.edu

585-275-4911

Study Officials

• Jonathan Friedberg, md

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 18, 2007
• First Posted: October 22, 2007
• Study Start: October 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: October 1, 2009
• Last Updated: August 6, 2015
• Results First Posted: June 6, 2011

Record last verified: 2015-07

Locations

US (3)