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

NCT00262860 | Completed Phase 2 Results DMC

• 6 other identifiers: CDR0000448635URCC-U9404URCC-RSRB-10368MILLENNIUM-VEL-03-079LILLY-B9E-US-X433DFCI-04388
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Lymphoma

Keywords

recurrent adult Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• 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).

  21 Days/course for up to 2 courses

Secondary Outcomes (2)

• Change in Proteasome Activity Compared to Baseline (Cycle 1)

  baseline to 2 hours

• Change in Proteasome Activity Compared to Baseline (Cycle 2)

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

Study Arms (1)

Bortezomib, Gemcitabine Hdrochloride

EXPERIMENTAL

Drug: bortezomib; Drug: gemcitabine hydrochloride

Interventions

bortezomib DRUG

Bortezomib, Gemcitabine Hdrochloride

gemcitabine hydrochloride DRUG

Bortezomib, Gemcitabine Hdrochloride

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (2)

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

Boston, Massachusetts, 02115, United States

Location

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

Rochester, New York, 14642, United States

Location

Related Publications (1)

• 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.

  PMID: 18504251 RESULT

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease

Interventions

Bortezomib; Gemcitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

Trial was stopped early by the Data Safety Monitoring Committee due to unexpected toxicity with no improvement in the response rate compared with gemcitabine alone. Trial was prespecified to be stopped early if these criteria were met.

Results Point of Contact

• Title: Jonathan W. Friedberg
• Organization: University of Rochester

jonathan_friedberg@urmc.rochester.edu

585-273-4150

Study Officials

• Jonathan W. Friedberg, MD

  James P. Wilmot Cancer Center

  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: December 6, 2005
• First Posted: December 7, 2005
• Study Start: April 1, 2005
• Primary Completion: May 1, 2008
• Last Updated: May 9, 2016
• Results First Posted: March 28, 2016

Record last verified: 2016-03

Locations

US (2)