Bortezomib and Gemcitabine Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

bortezomib

gemcitabine hydrochloride

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma Recurrent or refractory disease after prior standard combination chemotherapy Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 1 cm by physical exam or imaging studies No history of non-Hodgkin's lymphoma No history of other hematological malignancy PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,000/mm^3 Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert's disease or involvement by Hodgkin's lymphoma) AST ≤ 3 times ULN (unless due to involvement by Hodgkin's lymphoma) Renal Creatinine clearance ≥ 30 mL/min Cardiovascular Ejection fraction ≥ 40% by MUGA or echocardiogram (in patients with a history of cardiac disease) Pulmonary Must not require supplemental oxygen therapy Immunologic No known HIV infection No uncontrolled bacterial, viral, or fungal infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy requiring therapy No peripheral neuropathy ≥ grade 2 within the past 14 days No hypersensitivity to boron No hypersensitivity to mannitol PRIOR CONCURRENT THERAPY: Biologic therapy More than 30 days since prior monoclonal antibody therapy for Hodgkin's lymphoma More than 6 months since prior autologous stem cell transplantation No prior allogeneic stem cell transplantation No concurrent sargramostim (GM-CSF) No concurrent pegfilgrastim or filgrastim (G-CSF) No concurrent interleukin-11(oprelvekin) Chemotherapy See Disease Characteristics More than 30 days since prior chemotherapy for Hodgkin's lymphoma No prior treatment with gemcitabine hydrochloride Endocrine therapy More than 30 days since prior corticosteroid therapy for Hodgkin's lymphoma No concurrent corticosteroid therapy Radiotherapy More than 30 days since prior radiotherapy for Hodgkin's lymphoma Other No prior treatment with bortezomib More than 14 days since prior investigational drugs No other concurrent investigational agents

Sites / Locations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
James P. Wilmot Cancer Center at University of Rochester Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bortezomib, Gemcitabine Hdrochloride

Arm Description

Outcomes

Primary Outcome Measures

Response Rate After 2 Courses of Therapy

Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV).

Secondary Outcome Measures

Change in Proteasome Activity Compared to Baseline (Cycle 1)

Peripheral blood (40 ml) was collected on cycle 1, day 1 of prebortezomib at baseline and 2 hrs post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.

Change in Proteasome Activity Compared to Baseline (Cycle 2)

Peripheral blood (40 ml) was collected at baseline and 1-2 weeks after cycle 2, day 11 post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.

Full Information

NCT ID

NCT00262860

First Posted

December 6, 2005

Last Updated

March 30, 2016

Sponsor

University of Rochester

1. Study Identification

Unique Protocol Identification Number

NCT00262860

Brief Title

Bortezomib and Gemcitabine Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

Official Title

Phase II Pilot Study of Bortezomib (VELCADE®) and Gemcitabine for Patients With Relapsed or Refractory Hodgkin's Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Completed

Study Start Date

April 2005 (undefined)

Primary Completion Date

May 2008 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rochester

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with gemcitabine hydrochloride may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib together with gemcitabine hydrochloride works in treating patients with relapsed or refractory Hodgkin's lymphoma.

Detailed Description

OBJECTIVES: Primary Determine the overall response rate (partial and complete response) in patients with relapsed or refractory Hodgkin's lymphoma treated with bortezomib and gemcitabine hydrochloride. Secondary Determine the safety and toxic effects of this regimen in these patients. Determine the time to progression in patients treated with this regimen. Correlate NF-kB inhibition and proteasome activity with response in patients treated with this regimen. OUTLINE: This is a multicenter, pilot 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 for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Bortezomib, Gemcitabine Hdrochloride

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

bortezomib

Intervention Type

Drug

Intervention Name(s)

gemcitabine hydrochloride

Primary Outcome Measure Information:

Title

Response Rate After 2 Courses of Therapy

Description

Response was evaluated after two cycles of therapy using the 1999 Cheson response criteria. All responses were based on CT scans. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. For patients who had FDG-PET imaging, metabolic response was defined as a decrease in the standardized uptake value in target lesions (regions of abnormal FDG uptake on pretreatment FDG-PET images) to below three on posttreatment FDG-PET imaging). All PET scans were reviewed and interpreted by a single radiologist (SV).

Time Frame

21 Days/course for up to 2 courses

Secondary Outcome Measure Information:

Title

Change in Proteasome Activity Compared to Baseline (Cycle 1)

Description

Peripheral blood (40 ml) was collected on cycle 1, day 1 of prebortezomib at baseline and 2 hrs post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.

Time Frame

baseline to 2 hours

Title

Change in Proteasome Activity Compared to Baseline (Cycle 2)

Description

Peripheral blood (40 ml) was collected at baseline and 1-2 weeks after cycle 2, day 11 post-bortezomib treatment. The samples were refrigerated at 4C and processed within 36 h of collection. Frozen cell lysates were thawed and the proteasome activity in 10 microliters was determined using a spectroflourometric 20S proteasome assay kit. Samples were run in triplicate on two separate days. The percent change between baseline and 2 hrs (day1, cycle 1) was calculated.

Time Frame

baseline and 1-2 weeks after cycle 2, day 11

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma Recurrent or refractory disease after prior standard combination chemotherapy Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 1 cm by physical exam or imaging studies No history of non-Hodgkin's lymphoma No history of other hematological malignancy PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,000/mm^3 Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) (unless due to Gilbert's disease or involvement by Hodgkin's lymphoma) AST ≤ 3 times ULN (unless due to involvement by Hodgkin's lymphoma) Renal Creatinine clearance ≥ 30 mL/min Cardiovascular Ejection fraction ≥ 40% by MUGA or echocardiogram (in patients with a history of cardiac disease) Pulmonary Must not require supplemental oxygen therapy Immunologic No known HIV infection No uncontrolled bacterial, viral, or fungal infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy requiring therapy No peripheral neuropathy ≥ grade 2 within the past 14 days No hypersensitivity to boron No hypersensitivity to mannitol PRIOR CONCURRENT THERAPY: Biologic therapy More than 30 days since prior monoclonal antibody therapy for Hodgkin's lymphoma More than 6 months since prior autologous stem cell transplantation No prior allogeneic stem cell transplantation No concurrent sargramostim (GM-CSF) No concurrent pegfilgrastim or filgrastim (G-CSF) No concurrent interleukin-11(oprelvekin) Chemotherapy See Disease Characteristics More than 30 days since prior chemotherapy for Hodgkin's lymphoma No prior treatment with gemcitabine hydrochloride Endocrine therapy More than 30 days since prior corticosteroid therapy for Hodgkin's lymphoma No concurrent corticosteroid therapy Radiotherapy More than 30 days since prior radiotherapy for Hodgkin's lymphoma Other No prior treatment with bortezomib More than 14 days since prior investigational drugs No other concurrent investigational agents

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jonathan W. Friedberg, MD

Organizational Affiliation

James P. Wilmot Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

James P. Wilmot Cancer Center at University of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18504251

Citation

Mendler JH, Kelly J, Voci S, Marquis D, Rich L, Rossi RM, Bernstein SH, Jordan CT, Liesveld J, Fisher RI, Friedberg JW. Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma. Ann Oncol. 2008 Oct;19(10):1759-64. doi: 10.1093/annonc/mdn365. Epub 2008 May 25.

Results Reference

result

Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial