Clinical trial NCT00262860: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent adult Hodgkin lymphoma
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2005-12-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Response Rate After 2 Courses of Therapy
timeFrame: 21 Days/course for up to 2 courses
Secondary outcomes:
measure: Change in Proteasome Activity Compared to Baseline (Cycle 1)
timeFrame: baseline to 2 hours
measure: Change in Proteasome Activity Compared to Baseline (Cycle 2)
timeFrame: baseline and 1-2 weeks after cycle 2, day 11
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Jonathan W. Friedberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.