Trial Outcomes & Findings for Bortezomib and Gemcitabine Hydrochloride in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma (NCT NCT00262860)

NCT ID: NCT00262860

Last Updated: 2016-05-09

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 18 participants
• Primary outcome timeframe: 21 Days/course for up to 2 courses
• Results posted on: 2016-05-09

Participant Flow

Participant milestones

Measure	Bortezomib, Gemcitabine Hydrochloride bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Overall Study STARTED	18
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Bortezomib, Gemcitabine Hydrochloride bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Overall Study Adverse Event	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Bortezomib, Gemcitabine Hydrochloride n=18 Participants bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Age, Continuous	36 years n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race/Ethnicity, Customized White	16 participants n=5 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants
Region of Enrollment United States	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 21 Days/course for up to 2 courses

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).

Outcome measures

Measure	Bortezomib, Gemcitabine Hydrochloride n=18 Participants bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Response Rate After 2 Courses of Therapy	4 participants

SECONDARY outcome

Timeframe: baseline to 2 hours

Population: Samples were not collected on one patient, so only 17 patients were analyzed.

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.

Outcome measures

Measure	Bortezomib, Gemcitabine Hydrochloride n=17 Participants bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Change in Proteasome Activity Compared to Baseline (Cycle 1)	-50 Percentage of change in proteosome activ Interval -77.0 to 39.0

SECONDARY outcome

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

Population: Samples were not collected on one patient, so only 17 patients were analyzed.

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.

Outcome measures

Measure	Bortezomib, Gemcitabine Hydrochloride n=17 Participants bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Change in Proteasome Activity Compared to Baseline (Cycle 2)	-57 percentage of change in proteosome activ Interval -92.0 to 223.0

Adverse Events

Bortezomib, Gemcitabine Hydrochloride

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bortezomib, Gemcitabine Hydrochloride n=18 participants at risk bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Blood and lymphatic system disorders neutropenia	27.8% 5/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders leukopenia	16.7% 3/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders thrombocytompenia	11.1% 2/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Hepatobiliary disorders elevated transaminases	16.7% 3/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Vascular disorders hyperglycemia	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
General disorders abdominal pain/cramps	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders lymphopenia	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Nervous system disorders headache/migraine	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Infections and infestations sepsis	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Vascular disorders DVT near line	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Skin and subcutaneous tissue disorders worsening leg ulcer	5.6% 1/18 • days 1 and 8 of each cycle of therapy, up to 2 months

Other adverse events

Measure	Bortezomib, Gemcitabine Hydrochloride n=18 participants at risk bortezomib gemcitabine hydrochloride Bortezomib was administered at a dose of 1 mg/m2 on days 1, 4, 8,and 11 of a 21-day schedule. Gemcitabine was administered at a dose of 800 mg/m2 on days 1 and 8 of the same 21-day schedule.
Blood and lymphatic system disorders neutropenia	27.8% 5/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders leukopenia	38.9% 7/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders thrombocytopenia	44.4% 8/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Hepatobiliary disorders elevated transaminases	22.2% 4/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Endocrine disorders hyperglycemia	16.7% 3/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Gastrointestinal disorders abdominal pain/cramps	11.1% 2/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders anemia	44.4% 8/18 • days 1 and 8 of each cycle of therapy, up to 2 months
General disorders pain	38.9% 7/18 • days 1 and 8 of each cycle of therapy, up to 2 months
Blood and lymphatic system disorders hypocalcemia	33.3% 6/18 • days 1 and 8 of each cycle of therapy, up to 2 months

Additional Information

Jonathan W. Friedberg

University of Rochester

Phone: 585-273-4150

Email: jonathan_friedberg@urmc.rochester.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place