A Phase I/II Trial of VELCADE & Gemcitabine for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00290706
• Collaborator: Eli Lilly and Company (Industry), Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Actual Duration (Months): 77
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: 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 stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with gemcitabine and to see how well they work in treating patients with relapsed or refractory B-cell or T-cell non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: bortezomib; Drug: gemcitabine hydrochloride	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate (complete and partial remission) in patients with relapsed or refractory aggressive B- or T-cell non-Hodgkin's lymphoma treated with gemcitabine hydrochloride and bortezomib.

• Determine the maximum tolerated dose of bortezomib when administered with gemcitabine hydrochloride in these patients.

Secondary

• Determine the time to treatment failure, duration of response, and overall survival of patients treated with this regimen.

• Determine the safety and tolerability of this regimen in these patients.

OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II, open-label study.

• Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes and bortezomib IV over 3-5 seconds on days 1 and 8. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity (DLT) OR the dose that at which 2 of 6 patients experience DLT.

• Phase II: Patients receive gemcitabine hydrochloride and bortezomib as in phase I at the MTD.

After completion of study therapy, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of Combination Bortezomib (VELCADE) and Gemcitabine Therapy for Patients With Relapsed or Refractory Aggressive B- and T-cell Non-Hodgkin's Lymphoma
• Actual Study Start Date: Apr 7, 2006
• Actual Primary Completion Date: Feb 11, 2011
• Actual Study Completion Date: Sep 5, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine 800 mg/m2 + Bortezomib IVP over 3-5 seconds Gemcitabine dose of 800 mg/m2 over 30 minutes followed by Bortezomib IVP given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.	Drug: bortezomib; Bortezomib 1.6mg/m2 on days 1 and 15 of each cycle, given over 3-5 seconds on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.; Other Names: Velcade® PS-341 ; Drug: gemcitabine hydrochloride; Gemcitabine dose of 800 mg/m2 over 30 minutes on day 1 and day 15 of each cycle every 28 days for up to 8 cycles.; Other Names: Gemzar®

Outcome Measures

Primary Outcome Measures

1. Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment. [At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8]

   Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission [CR] and Partial Remission [PR]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where: CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=> 50% decrease in SPD of the six largest dominant nodes or nodal masses

Secondary Outcome Measures

1. Time to Treatment Failure and Duration of Response [At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years]

   Time to treatment failure and duration of response will be measured by CT Scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

2. Overall Survival [Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years]

   Overall survival will be evaluated every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

3. Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy [During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment]

   Safety and tolerability of the study drugs will be assessed on Day 1 and on either Day 8 or Day 15 of each treatment cycle (1 Cycle - 28 days) while on active treatment; and 30 days post last treatment. Adverse Events that are experienced by patients, determined to be either grade 3 or grade 4 and at least possibly related to at least one of the study drugs as assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) will be collected. In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of B- or T-cell non-Hodgkin's lymphoma (NHL)

• Intermediate histology B-cell NHL, including any of the following:

• Diffuse large B-cell lymphoma

• Transformed large cell lymphoma

• Any T-cell NHL histology

• Cutaneous T-cell lymphoma (CTCL) or mycosis fungoides (MF) allowed

• Relapsed or refractory disease, defined as disease progressed after prior complete remission (CR), partial remission (PR), or stable disease (SD) to last therapy OR failure to achieve CR, PR, or SD after completion of last therapy

• Must have received 1-3 prior therapeutic regimens

• Cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (CHOP) AND cyclophosphamide, vincristine, and prednisone (CVP) OR CHOP with rituximab (CHOP-R) AND CVP with rituximab (CVP-R) is considered 1 regimen

• Monoclonal antibody (e.g., rituximab) given as maintenance therapy is considered 1 regimen

• Salvage chemotherapy followed by an autologous stem cell transplant is considered 1 regimen

• No more than 7 prior therapeutic regimens for patients with CTCL or MF

• No mantle cell lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy > 3 months

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• At least 50,000/mm^3 if documented bone marrow involvement

• Hemoglobin ≥ 8.0 g/dL

• AST and ALT ≤ 3 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 3 times ULN

• Bilirubin ≤ 2 times ULN

• Creatinine ≤ 2.0 mg/dL

• No known history of HIV infection

• No other active infection

• No uncontrolled hypertension

• No peripheral neuropathy ≥ grade 2 within the past 2 weeks

• No myocardial infarction within the past 6 months

• No New York Heart Association class III or IV heart failure

• No uncontrolled angina

• No severe uncontrolled ventricular arrhythmias

• No acute ischemia or active conduction system abnormalities by ECG

• No hypersensitivity to bortezomib, boron, or mannitol

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier-method contraception

• No serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• Prior autologous and/or allogeneic stem cell transplantation allowed

• More than 3 weeks since prior chemotherapy, radiotherapy, or immunotherapy

• More than 3 weeks since prior systemic biologic anticancer therapy

• More than 3 weeks since prior systemic corticosteroids (e.g., oral prednisone > 10 mg per day)

• More than 2 weeks since prior investigational drug

• No prior bortezomib or gemcitabine hydrochloride

• No other concurrent systemic cytotoxic chemotherapy or investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois	United States	60611
3	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• Northwestern University
• Eli Lilly and Company
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Leo Gordon, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT00290706
• Other Study ID Numbers: NU 04H4; NU 04H4; VEL-03-082; STU00007425
• First Posted: Feb 13, 2006
• Last Update Posted: May 28, 2019
• Last Verified: May 1, 2019

• Keywords provided by Northwestern University: recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 3 follicular lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Gemcitabine; Bortezomib

Study Results

Participant Flow

Recruitment Details	The study opened for accrual to phase I on September 26, 2005 with first patient treated April 7 2006.The study was closed on October 17 2007 to phase I and opened to phase II on December 18 2007. The study closed permanently March 9 2011 with a total accrual of 32 patients treated on the study before reaching the total accrual goal.

Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Period Title: Overall Study
STARTED	5	6	7	14
Attempted1st Cycle	5	6	7	14
Reached 1st Response/Cycle 3	0	0	1	2
COMPLETED	0	0	1	2
NOT COMPLETED	5	6	6	12

Baseline Characteristics

Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15	Total
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.	Total of all reporting groups
Overall Participants	5	6	7	14	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 60%	5 83.3%	5 71.4%	9 64.3%	22 68.8%
>=65 years	2 40%	1 16.7%	2 28.6%	5 35.7%	10 31.3%
Sex: Female, Male (Count of Participants)
Female	1 20%	4 66.7%	4 57.1%	5 35.7%	14 43.8%
Male	4 80%	2 33.3%	3 42.9%	9 64.3%	18 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	1 14.3%	2 14.3%	3 9.4%
Not Hispanic or Latino	5 100%	6 100%	6 85.7%	12 85.7%	29 90.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 7.1%	1 3.1%
Asian	0 0%	0 0%	0 0%	1 7.1%	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	2 33.3%	2 28.6%	1 7.1%	5 15.6%
White	5 100%	4 66.7%	5 71.4%	11 78.6%	25 78.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	6 100%	7 100%	14 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate in Patients With Relapsed or Refractory B- and T-cell NHL With Gemcitabine and Bortezomib Combination Treatment.
Description	Response rate in patients with relapsed or refractory B- and T-cell NHL with Gemcitabine and Bortezomib combination treatment will be defined as the number of patients with Complete Remission [CR] and Partial Remission [PR]. CT scans at screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8 assessed by the Response Criteria for Non-hodgkins Lymphoma will be used to determine response where: CR=Complete disappearance of all detectable clinical and radiographic evidence of disease PR=> 50% decrease in SPD of the six largest dominant nodes or nodal masses
Time Frame	At screening and after completing cycle 3, cycle 6 and 30 days after Cycle 8

Outcome Measure Data

Analysis Population Description

Patients must complete 3 cycles of treatment to be evaluable for this outcome measure. Only 3 patients reached Cycle 3 and the study closed before accrual was met due to lack of efficacy. Below shows response of patients that reached Cycle 3 and is not a reflection of response rate.

Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Measure Participants	0	0	1	2
Number [participants]	1 20%	2 33.3%

2. Secondary Outcome

Title	Time to Treatment Failure and Duration of Response
Description	Time to treatment failure and duration of response will be measured by CT Scan at screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years
Time Frame	At screening and after completing cycle 3, cycle 6 and 30 days after cycle 8, then every 6 months for 3 years

Outcome Measure Data

Analysis Population Description

Study was terminated due to lack of efficacy. Data not collected for analysis of outcome measure.

Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Measure Participants	0	0	0	0

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival will be evaluated every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years
Time Frame	Every 6 months while on treatment and then every 6 months while off of treatment for up to 3 years

Outcome Measure Data

Analysis Population Description

The study was terminated early due to lack of efficacy. Data not collect for analysis of this outcome measure.

Arm/Group Title	Gemcitabine 800 mg/m2 + Bortezomib IVP Over 3-5 Seconds
Arm/Group Description	Gemcitabine dose of 800 mg/m2 over 30 minutes followed by Bortezomib IVP given over 3-5 seconds on either Day 1/Day 8 or Day 1/Day 15 of each cycle every 28 days for up to 8 cycles. Bortezomib: Bortezomib either 1.3 mg/m2 or 1.6mg/m2 on either Day 1/Day 8 or Day 1/Day 15 of each cycle, given over 3-5 seconds every 28 days for up to 8 cycles. Gemcitabine hydrochloride: Gemcitabine dose of 800 mg/m2 over 30 minutes on either Day 1/Day 8 or Day 1/Day 15 of each cycle every 28 days for up to 8 cycles.
Measure Participants	0

4. Secondary Outcome

Title	Evaluate Safety and Tolerability of Bortezomib and Gemcitabine Therapy
Description	Safety and tolerability of the study drugs will be assessed on Day 1 and on either Day 8 or Day 15 of each treatment cycle (1 Cycle - 28 days) while on active treatment; and 30 days post last treatment. Adverse Events that are experienced by patients, determined to be either grade 3 or grade 4 and at least possibly related to at least one of the study drugs as assessed according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) will be collected. In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Time Frame	During treatment through a maximum of 8 Cycles (1 Cycle = 28 Days) and 30 days post last treatment

Outcome Measure Data

Analysis Population Description

The study was terminated before total accrual was met due to lack of efficacy. Data was not collected for analysis for this outcome measure

Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8	Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
Measure Participants	0	0	0	0

Adverse Events

Time Frame	Adverse events were collected from the start of treatment through 30 days post treatment. The study was designed for a maximum of 8 Cycles of treatment (1 Cycle = 28 days) and the range of cycles attemted by any patient was 1 - 8.
Arm/Group Title	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2		Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
Arm/Group Description	Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.3 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.		Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.		Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 8 of a 28 day Cycle for up to 8 cycles of treatment.		Patients are treated with Gemcitabine 800mg/m2 IV over 30 minutes and Bortezomib 1.6 mg/m2 IVP over 3-5 seconds on Day 1 and Day 15 of a 28 day Cycle for up to 8 cycles of treatment.
All Cause Mortality
	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2		Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		6/6 (100%)		7/7 (100%)		11/14 (78.6%)
Serious Adverse Events
	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2		Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		2/6 (33.3%)		3/7 (42.9%)		6/14 (42.9%)
Blood and lymphatic system disorders
Anemia	0/5 (0%)		2/6 (33.3%)		0/7 (0%)		0/14 (0%)
Cardiac disorders
Hypertension	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Gastrointestinal disorders
Vomiting	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
General disorders
Multi organ failure - death	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Fever	1/5 (20%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Infections and infestations
Pneumonia leading to death	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Infection NOS	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Pneumonia	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Sepsis	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Bacteremia	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Neutropenia	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Metabolism and nutrition disorders
Hyponatremia	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progressive disease - death	2/5 (40%)		0/6 (0%)		1/7 (14.3%)		2/14 (14.3%)
Nervous system disorders
Headache	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Renal and urinary disorders
Renal Failure	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Rectal bleeding	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Skin and subcutaneous tissue disorders
Rash	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.3 mg/m2		Cohort 1 -Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D8		Phase II Gemcitabine 800 mg/m2 + Bortezomib 1.6 mg/m2 D1+D15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		6/6 (100%)		7/7 (100%)		14/14 (100%)
Blood and lymphatic system disorders
Hemoglobin decreased (Anemia)	4/5 (80%)		3/6 (50%)		5/7 (71.4%)		9/14 (64.3%)
Neutrophil decreased (neutropenia)	2/5 (40%)		2/6 (33.3%)		3/7 (42.9%)		1/14 (7.1%)
Lymphocyte Count Decreased	3/5 (60%)		2/6 (33.3%)		4/7 (57.1%)		3/14 (21.4%)
Platelet Decrease (Thrombocytopenia)	4/5 (80%)		3/6 (50%)		5/7 (71.4%)		5/14 (35.7%)
Edema	1/5 (20%)		3/6 (50%)		0/7 (0%)		0/14 (0%)
Edema in Limbs	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		2/14 (14.3%)
Edema in Head and Neck	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Cardiac disorders
Hypertension	0/5 (0%)		2/6 (33.3%)		0/7 (0%)		1/14 (7.1%)
Hypotension	0/5 (0%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Atrial Fibrillation	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Tachycardia	1/5 (20%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Endocrine disorders
Hot flashes/Flashes	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Gastrointestinal disorders
Anorexia	2/5 (40%)		0/6 (0%)		1/7 (14.3%)		1/14 (7.1%)
Constipation	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		3/14 (21.4%)
Dehydration	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Diarrhea	2/5 (40%)		1/6 (16.7%)		1/7 (14.3%)		5/14 (35.7%)
Abdominal distension/bloating	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Dyspepsia (Heartburn)	1/5 (20%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Nausea	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		7/14 (50%)
Dysgeusia (Taste Alteration)	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Vomiting	1/5 (20%)		1/6 (16.7%)		0/7 (0%)		4/14 (28.6%)
Pain in Throat	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Pain in Abdomen (Not otherwise specified)	0/5 (0%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
General disorders
Fatigue	4/5 (80%)		4/6 (66.7%)		3/7 (42.9%)		8/14 (57.1%)
Fever	3/5 (60%)		2/6 (33.3%)		2/7 (28.6%)		1/14 (7.1%)
Sweating	1/5 (20%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Weight Loss	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		1/14 (7.1%)
Weight gain	0/5 (0%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Bruising	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Pain in Bones	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Pain (Not otherwise specified)	0/5 (0%)		2/6 (33.3%)		1/7 (14.3%)		2/14 (14.3%)
Infections and infestations
Shingles	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Angular Cheilitis	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Pneumonia	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Infection in Leg	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Bronchopneumonia	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Sinus Infection	0/5 (0%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Urinary Tract Infection	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Oral Ulcer	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Infection (Not otherwise specified)	0/5 (0%)		0/6 (0%)		2/7 (28.6%)		0/14 (0%)
Metabolism and nutrition disorders
Increased LDH	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		1/14 (7.1%)
Alkaline Phosphatase	2/5 (40%)		3/6 (50%)		1/7 (14.3%)		3/14 (21.4%)
Transaminase Increased	1/5 (20%)		3/6 (50%)		1/7 (14.3%)		3/14 (21.4%)
ALT Increased	1/5 (20%)		1/6 (16.7%)		0/7 (0%)		1/14 (7.1%)
AST Increased	2/5 (40%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Albumin, Serum-Low	2/5 (40%)		2/6 (33.3%)		1/7 (14.3%)		3/14 (21.4%)
Bilirubin (hyperbilirubinemia)	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Bicarbonate-Low	1/5 (20%)		1/6 (16.7%)		1/7 (14.3%)		0/14 (0%)
Creatinine	3/5 (60%)		2/6 (33.3%)		1/7 (14.3%)		2/14 (14.3%)
Calcium, Serum High	0/5 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/14 (0%)
Glucose, Serum-High	4/5 (80%)		1/6 (16.7%)		1/7 (14.3%)		7/14 (50%)
Glucose, Serum-Low	1/5 (20%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Magnesium, Serum-Low	1/5 (20%)		0/6 (0%)		0/7 (0%)		3/14 (21.4%)
Phosphate, Serum-Low	0/5 (0%)		0/6 (0%)		0/7 (0%)		2/14 (14.3%)
Potassium, Serum-High	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		2/14 (14.3%)
Potassium, Serum-Low	2/5 (40%)		1/6 (16.7%)		0/7 (0%)		1/14 (7.1%)
Sodium, Serum-High	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Sodium, Serum-Low	1/5 (20%)		1/6 (16.7%)		1/7 (14.3%)		0/14 (0%)
Uric Acid, Serum-High	2/5 (40%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Muscle Weakness	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Pain in Back	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Pain in Extremities	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Nervous system disorders
Sensory Neuropathy	1/5 (20%)		1/6 (16.7%)		1/7 (14.3%)		8/14 (57.1%)
Pain	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Confusion	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Dizziness	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Depression	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Tremor	0/5 (0%)		0/6 (0%)		1/7 (14.3%)		0/14 (0%)
Neuralgia	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Headache	1/5 (20%)		1/6 (16.7%)		0/7 (0%)		1/14 (7.1%)
Renal and urinary disorders
Hemorrhage - Urinary	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Incontinence	1/5 (20%)		0/6 (0%)		0/7 (0%)		0/14 (0%)
Reproductive system and breast disorders
Pain in Pelvis	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	1/5 (20%)		2/6 (33.3%)		2/7 (28.6%)		2/14 (14.3%)
Dyspnea (Shortness of Breath)	2/5 (40%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Pleural Effusion	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Skin (Not otherwise specified)	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Nasal Ulcer	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Petechiae	0/5 (0%)		1/6 (16.7%)		0/7 (0%)		0/14 (0%)
Pruritus/Itching	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)
Rash	1/5 (20%)		1/6 (16.7%)		1/7 (14.3%)		0/14 (0%)
Pain in Skin	0/5 (0%)		0/6 (0%)		0/7 (0%)		1/14 (7.1%)

Limitations/Caveats

The study was terminated before the accrual goal was met as it was determined that the study lacked efficacy. Most patients did not reach 3 cycles of treatment in order to be evaluable for response.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.