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

• Sponsor: University of Rochester (Other)
• Overall Status: Completed
• CT.gov ID: NCT00547534
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry), Cephalon (Industry)
• Enrollment: 31
• Locations: 3
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Drug: bortezomib; Drug: bendamustine; Drug: rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Bortezomib, Bendamustine and Rituximab for Patients With Relapsed or Refractory, Indolent or Mantle Cell Non-Hodgkin's Lymphoma
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lymphoma Subjects receiving protocol therapy Subjects that met all eligibility criteria and were treated with Bendamustine, Rituxan and Bortezomib.	Drug: bortezomib; 1.3 mg/m^2 on days 1, 4, 8, 11; Other Names: Velcade ; Drug: bendamustine; 90 mg/m^2 days 1 and 4; Other Names: Treanda ; Drug: rituximab; 375 mg/m^2 day 1; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Progression Free Survival at 2 Years [Two 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.

Secondary Outcome Measures

1. Toxicity of Drug Combination in the Subjects [Two years]

2. Overall Response Rate (ORR) [Two years]

   Overall response rate (ORR)to protocol treatment - Partial response, Complete response, etc.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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).

• History of solid organ transplantation, or post transplant lymphoproliferative disorder

• Patient has history of allogeneic stem cell transplantation.

• Patient has history of autologous stem cell transplantation or radioimmunotherapy within the previous 4 months.

• Patient has received any other investigational drugs within 14 days prior to enrollment

• History of, or clinically apparent CNS lymphoma

• Any clinically significant abnormality in screening blood chemistry, hematology, or urinalysis results that, in the judgment of the investigator, would impede adequate evaluation of adverse events and/or response to treatment, or that requires aggressive intervention

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nebraska Medical Center	Omaha	Nebraska	United States	68198
2	Cornell Wiell Medical College	New York	New York	United States	10021
3	University of Rochester Medical Center (James P. Wilmot Cancer Center)	Rochester	New York	United States	14642

Sponsors and Collaborators

• University of Rochester
• Millennium Pharmaceuticals, Inc.
• Cephalon

Investigators

• Principal Investigator: Jonathan Friedberg, md, University of Rochester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonathan Friedberg, Professor, University of Rochester
• ClinicalTrials.gov Identifier: NCT00547534
• Other Study ID Numbers: ULYM07054
• First Posted: Oct 22, 2007
• Last Update Posted: Aug 6, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Jonathan Friedberg, Professor, University of Rochester: Bortezomib; Bendamustine; Rituximab; Relapsed; Refractory; Mantle Cell; Indolent
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Bortezomib; Bendamustine Hydrochloride

Study Results

Participant Flow

Recruitment Details	Recruitment at the University of Rochester Medical Center, Weill Cornell Medical Center and the University of Nebraska began in October 2007 and ended in March 2009. Patients were recruited in a medial clinic setting.

Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were given study treatment.
Period Title: Overall Study
STARTED	30
COMPLETED	19
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were given study treatment.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 53.3%
>=65 years	14 46.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (20)
Sex: Female, Male (Count of Participants)
Female	8 26.7%
Male	22 73.3%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Progression Free Survival at 2 Years
Description	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.
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

Analysis was per protocol.

Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were treated.
Measure Participants	29
Number [Participants]	13 43.3%

2. Secondary Outcome

Title	Toxicity of Drug Combination in the Subjects
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were treated
Measure Participants	29
Number [Lymphoma Subjects]	13

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Overall response rate (ORR)to protocol treatment - Partial response, Complete response, etc.
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were treated.
Measure Participants	29
Number [Lymphoma Subjects]	13

Adverse Events

Time Frame	Two years
Arm/Group Title	Lymphoma Subjects
Arm/Group Description	Subjects that met all eligibility criteria and were given study treatment.
All Cause Mortality
	Lymphoma Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lymphoma Subjects
	Affected / at Risk (%)	# Events
Total	13/30 (43.3%)
Blood and lymphatic system disorders
Hypotension	2/30 (6.7%)	2
Endocrine disorders
Renal Failure	1/30 (3.3%)	1
Gastrointestinal disorders
Sepsis	1/30 (3.3%)	1
Liver Failure	1/30 (3.3%)	1
Dehydration	2/30 (6.7%)	2
General disorders
Fatigue	2/30 (6.7%)	2
Infections and infestations
Herpes zoster	2/30 (6.7%)	2
Nervous system disorders
Peripheral neuropathy	2/30 (6.7%)	2
Other (Not Including Serious) Adverse Events
	Lymphoma Subjects
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Cardiac disorders
Hypotension	6/30 (20%)	6
Shortness of breath	3/30 (10%)	3
Gastrointestinal disorders
Nausea	15/30 (50%)	15
Constipation	12/30 (40%)	12
Diarrhea	8/30 (26.7%)	8
Anorexia	3/30 (10%)	3
Stomach/abdominal pain	3/30 (10%)	3
General disorders
Fatigue	14/30 (46.7%)	14
Fever	12/30 (40%)	12
Rigors / chills	5/30 (16.7%)	5
Headache	4/30 (13.3%)	4
Pruritis	3/30 (10%)	3
Dizziness	3/30 (10%)	3
Infections and infestations
Cough	7/30 (23.3%)	7
Herpes zoster	4/30 (13.3%)	4
Allergic reaction	4/30 (13.3%)	4
Rash	3/30 (10%)	3
Musculoskeletal and connective tissue disorders
Pain	9/30 (30%)	9
Nervous system disorders
Peripheral neuropathy	14/30 (46.7%)	14

Limitations/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

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.