Bortezomib and Gemcitabine in Treating Patients With Relapsed Mantle Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT00377052
• Recruitment Status: Completed
• First Posted: September 15, 2006
• Last Update Posted: April 8, 2020
• Sponsor: NCIC Clinical Trials Group
• Information provided by (Responsible Party): Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Study Description

Brief Summary:

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. 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 help gemcitabine work better by making cancer cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine works in treating patients with relapsed mantle cell lymphoma.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: bortezomib; Drug: gemcitabine hydrochloride	Phase 2

Detailed Description:

OBJECTIVES:

• Determine the efficacy (response rate) of bortezomib and gemcitabine hydrochloride in patients with relapsed mantle cell lymphoma.
• Determine the toxicity of this regimen in these patients.
• Determine the time to progression and duration of response in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter study.

Patients receive bortezomib IV on days 1, 4, 8, and 11 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter until relapse/progression.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Bortezomib and Gemcitabine in Patients With Relapsed Mantle Cell Lymphoma
• Actual Study Start Date: June 14, 2006
• Actual Primary Completion Date: April 21, 2009
• Actual Study Completion Date: June 21, 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bortezomib + Gemcitabine	Drug: bortezomib; 1.0 mg/m2 IV; injection bolus (3-5 sec) Twice weekly x 2 weeks every three weeks; Drug: gemcitabine hydrochloride; 1000 mg/m2 IV; injection 30 minute infusion Once weekly x 2 weeks every three weeks

Outcome Measures

Primary Outcome Measures :

1. Objective tumor response (overall response rate with 95% confidence interval) [ Time Frame: each cycle ]
2. Time to progression at median time [ Time Frame: each cycle and every 3 months after treatment ]
3. Duration of response (median and range) [ Time Frame: each cycle and every 3 months after treatment ]
4. Rate of stable disease and progressive disease [ Time Frame: each cycle and every 3 months after treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma

  • Relapsed disease

• Not refractory to prior therapy

  • Must have received 1-3 prior systemic chemotherapy regimens AND has had no disease progression while receiving chemotherapy or within 1 month of last dose of most recent therapy

• Clinically and/or radiologically documented disease

  • At least 1 site of disease must be bidimensionally measurable by CT scan or MRI with ≥ 1 lesion meeting 1 of the following criteria:

    • Lymph nodes ≥ 1.5 cm x 1.5 cm by spiral CT scan
    • Non-nodal lesion ≥ 1 cm x 1 cm by MRI, CT scan, or physical exam
  • No nonmeasurable disease only
• No preexisting ascites or pleural effusion ≥ grade 2
• No known CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN
• AST or ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• LVEF ≥ 45% by echocardiogram or MUGA
• No history of allergic reactions attributed to compounds containing boron or mannitol
• No preexisting edema ≥ grade 2
• No preexisting neuropathy (sensory and/or pain) ≥ grade 2
• No preexisting shortness of breath ≥ grade 2
• No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years

• No other serious illness or medical condition that would preclude compliance with study requirements, including any of the following:

  • Serious uncontrolled infection

  • Uncontrolled or severe cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • New York Heart Association class III-IV heart failure
    • Uncontrolled angina
    • Clinically significant pericardial disease
    • Cardiac amyloidosis
  • Significant neurological disorder

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 weeks since prior chemotherapy
• No prior radioactive monoclonal antibody therapy
• No prior bortezomib
• No prior investigational therapy (except for flavopiridol)
• No prior radiotherapy to > 25% of functioning bone marrow

• At least 4 weeks since prior radiotherapy and recovered

  • Low-dose, nonmyelosuppressive radiotherapy may be allowed
• At least 2 weeks since prior major surgery
• No other concurrent anticancer therapy
• No concurrent corticosteroids
• No other concurrent cytotoxic chemotherapy
• No other concurrent investigational agents

Contacts and Locations

Locations

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Nova Scotia

QEII Health Sciences Center

Halifax, Nova Scotia, Canada, B3H 1V7

QEII, CCR, Hematology Research

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Program

London, Ontario, Canada, N6A 4L6

Odette Cancer Centre

Toronto, Ontario, Canada, M4N 3M5

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

McGill University - Dept. Oncology

Montreal, Quebec, Canada, H2W 1S6

Canada, Saskatchewan

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada, S7N 4H4

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

• Principal Investigator: C. Tom Kouroukis, MD; Margaret and Charles Juravinski Cancer Centre

More Information

Publications of Results:

Kouroukis CT, Fernandez LA, Crump M, Gascoyne RD, Chua NS, Buckstein R, Turner R, Assouline S, Klasa RJ, Walsh W, Powers J, Eisenhauer E. A phase II study of bortezomib and gemcitabine in relapsed mantle cell lymphoma from the National Cancer Institute of Canada Clinical Trials Group (IND 172). Leuk Lymphoma. 2011 Mar;52(3):394-9. doi: 10.3109/10428194.2010.546015. Erratum in: Leuk Lymphoma. 2011 Jun;52(6):1160. Gascoyne, Randy D [added].

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00377052
• Other Study ID Numbers: I172; CAN-NCIC-IND172 ( Registry Identifier: PDQ ); ORTHO-CAN-NCIC-IND172 ( Other Identifier: Ortho Biotech ); CDR0000493021 ( Other Identifier: PDQ ); B9E-CA-0485 ( Other Identifier: Lilly )
• First Posted: September 15, 2006
• Last Update Posted: April 8, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):

recurrent mantle cell lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Mantle-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Gemcitabine; Bortezomib; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs