Safety and Efficacy Study of Single Weekly Bortezomib in Newly Diagnosed Multiple Myeloma

• Sponsor: Boston VA Research Institute, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01090921
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 50
• Locations: 11
• Arm: 1
• Duration (Months): 94
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a research study to see if a new drug called bortezomib is useful to treat multiple myeloma in people who are newly diagnosed, and have not yet received treatment for their disease. VELCADE® (bortezomib) for Injection is a drug under development by Millennium Pharmaceuticals, Inc.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bortezomib	Phase 2

Detailed Description

This study is a multi-site study which will enroll up to 50 patients with multiple myeloma who have not had prior treatment.

Prior to starting treatment individuals will be evaluated to determine if they are eligible to participate in the study. There are certain prestudy test that are required: physical exam, blood tests, ECG, chest x-ray, skeletal survey, bone marrow aspirate and biopsy to confirm the diagnosis of multiple myeloma and to determine baseline health status.

Before beginning each treatment cycle and at the end of the study, patients will have protein studies (including blood and urine) to see if they are responding to the treatment. Before each weekly treatment cycle patients will also have blood tests for red and white blood cells and platelets, and blood chemistry tests for electrolytes, kidney and liver function, calcium and blood sugar.

Patients may receive up to 6 cycles of treatment. At the end of the study, individuals who have responded to treatment will be seen every two months to check for disease progression.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study to Evaluate Efficacy and Safety of Single Weekly Administration of Bortezomib in Newly Diagnosed Multiple Myeloma
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Single-Arm Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks.

Drug: Bortezomib; Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.; Other Names: Velcade

Outcome Measures

Primary Outcome Measures

1. Number of Participants at Each Response Category (Stable Disease, Minimal Response, Partial Response, Very Good Partial Response, Near Complete Response/Complete Resonse) [Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.]

   To evaluate the response rate for weekly administered bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.

Secondary Outcome Measures

1. Number of Participants With Dose Reductions in Bortezomib, Dexamethasone or Both [Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.]

   To evaluate the toxicity (safety and tolerability) of weekly bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis of multiple myeloma based on standard criteria.

2. Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of > 1Gm/dL and/or urine monoclonal immunoglobulin spike of > 200mg/24 hours.

3. Non-secretors must have measurable protein by Freelite or measurable disease such as plasmacytoma to be eligible.

4. Patient must not have been previously treated with chemotherapy. Prior treatment of hypercalcemia with corticosteroids, or bisphosphonates does not disqualify the patient.

5. Patient must be ineligible for autologous stem cell transplant due to one or more of the following reasons:

• Age>65

• Impaired renal function (creatinine≥2.0 mg/dL)

• Impaired pulmonary function (DLCO≤50%)

• Poor performance status (KPS≤80)

• Other prohibitive comorbid disorder

• 5b. Patients≥60 who decline autologous stem cell transplant are eligible for this study.

• 5c. Patients who are eligible but wish to postpone autologous stem cell transplant are eligible for this study.

1. Karnofsky performance status>50

2. Patients treated with local radiotherapy with or without a brief exposure to steroids are eligible. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed, followed by a four week wash out period Spot RT to ≤3 vertebrae acceptable prior to entry.

3. Meets the following pretreatment laboratory criteria at Baseline (Within 14 days prior to study drug administration):

4. Platelet count>50x10^{9/L or, if the bone marrow is extensively infiltrated,>30x10}9/L

5. Hemoglobin>8.0G/dL

6. Absolute neutrophil count >1.0x10^{9/L or, if the bone marrow is extensively infiltrated, >0.5x10}9/L

7. Meets the following pretreatment laboratory criteria for liver function tests at the screening visit conducted within 14 days of registration

8. AST (SGOT): <3 times the upper limit of institutional laboratory normal

9. ALT (SGPT): <3 times the upper limit of institutional laboratory normal

10. Total bilirubin: <2 times the upper limit of institutional laboratory normal, unless clearly related to the disease

11. Women with child-bearing potential should be practicing an adequate form of contraception, as judged by the investigator (i.e. birth control pills, double barrier method, abstinence, etc.) or be surgically sterile or 12 months post-menopausal. Male subject agrees to use an acceptable method for contraception for the duration of the study.

12. Age 18 years or older

13. Has given voluntary written informed consent.

Exclusion Criteria:

1. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)

2. Plasma cell leukemia

3. Impaired kidney function requiring dialysis, patients on hemodialysis are excluded

4. Receiving steroids >the equivalent of 10mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosis, rheumatoid arthritis

5. Infection not controlled by antibiotics

6. HIV infection. Patients should provide consent for HIV testing according to the institution's standard practice

7. Known active hepatitis B or C

8. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

9. Second malignancy requiring concurrent treatment

10. Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol

11. Positive pregnancy test in women of childbearing potential

12. Patient has hypersensitivity to boron or mannitol.

13. Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.

14. Patient has received other investigational drugs with 14 days before enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Little Rock VA Medical Center	Little Rock	Arkansas	United States	72205
2	West Los Angeles VA Medical Center	Los Angeles	California	United States	90073
3	San Francisco VA Medical Center	San Francisco	California	United States	94121
4	Eastern Colorado Health Care System	Denver	Colorado	United States	80220
5	West Haven VA Medical Center	West Haven	Connecticut	United States	06516
6	Tampa VA Medical Center	Tampa	Florida	United States	33612
7	Atlanta VA Medical Center	Atlanta	Georgia	United States	30033
8	VA Boston Healthcare System	Jamaica Plain	Massachusetts	United States	02130
9	Kansas City VA Medical Center	Kansas City	Missouri	United States	64128
10	Pittsburgh VA Medical Center	Pittsburgh	Pennsylvania	United States	15240
11	Michael E. DeBakey VA Medical Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Boston VA Research Institute, Inc.
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Nikhil C. Munshi, M.D., Boston VA Research Institute, Inc.
• Study Chair: Saem Lee, Boston VA Research Institute, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nikhil Munshi, M.D., Principal Invesetigator -- Coordinating Site, Boston VA Research Institute, Inc.
• ClinicalTrials.gov Identifier: NCT01090921
• Other Study ID Numbers: X05153
• First Posted: Mar 23, 2010
• Last Update Posted: Sep 9, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Nikhil Munshi, M.D., Principal Invesetigator -- Coordinating Site, Boston VA Research Institute, Inc.: Multiple Myeloma; Bortezomib; Newly diagnosed; Newly diagnosed Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Bortezomib and Dexamethasone
Arm/Group Description	Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks. Bortezomib: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
Period Title: Overall Study
STARTED	50
COMPLETED	23
NOT COMPLETED	27

Baseline Characteristics

Arm/Group Title	Bortezomib and Dexamethasone
Arm/Group Description	Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks. Bortezomib: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
Overall Participants	50
Age, Customized (years) [Mean (Full Range) ]
Age	70.9
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	50 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	50 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants at Each Response Category (Stable Disease, Minimal Response, Partial Response, Very Good Partial Response, Near Complete Response/Complete Resonse)
Description	To evaluate the response rate for weekly administered bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.
Time Frame	Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib and Dexamethasone
Arm/Group Description	Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks. Bortezomib: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
Measure Participants	50
Complete Response/ near Complete Response	6 12%
Very Good Partial Response	13 26%
Partial Response	15 30%
Minimal Response	5 10%
Stable Disease	4 8%
Unevaluable	7 14%

2. Secondary Outcome

Title	Number of Participants With Dose Reductions in Bortezomib, Dexamethasone or Both
Description	To evaluate the toxicity (safety and tolerability) of weekly bortezomib + dexamethasone in patients with newly diagnosed multiple myeloma who are ineligible for transplant or who are eligible but wish to postpone autologous stem cell transplant.
Time Frame	Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib and Dexamethasone
Arm/Group Description	Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks. Bortezomib: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
Measure Participants	50
Bortezomib reductions	8 16%
Dexamethasone reductions	14 28%
Bortezomib and Dexamethasone reductions	4 8%

Adverse Events

Time Frame	Data was collected for each subject for the duration of the participation in the study, which was an average of 4.8 cycles.
Arm/Group Title	Bortezomib and Dexamethasone
Arm/Group Description	Bortezomib is administered at a dose of 1.6mg/m2 IV push over 3 to 5 seconds. Treatment is administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone is also administered at a dose of 40mg daily on day of and day after each dose of Bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone. The study duration for a given subject will be approximately 30 weeks. Bortezomib: Bortezomib will be administered at a dose of 1.6 mg/m2 IV push. Treatment will be administered once a week for four weeks followed by one week off. This 5 week period is considered a treatment cycle. Dexamethasone will also be administered at a dose of 40mg on the day of and day after each dose of bortezomib, with a dose reduction to 20mg on the same schedule if the patient cannot tolerate the higher dose of dexamethasone.
All Cause Mortality
	Bortezomib and Dexamethasone
	Affected / at Risk (%)	# Events
Total	6/50 (12%)
Serious Adverse Events
	Bortezomib and Dexamethasone
	Affected / at Risk (%)	# Events
Total	28/50 (56%)
Blood and lymphatic system disorders
Anemia	2/50 (4%)	2
Thrombocytopenia	1/50 (2%)	1
Lymphopenia	9/50 (18%)	9
Endocrine disorders
Hyperglycemia	9/50 (18%)	9
Gastrointestinal disorders
Diarrhea	2/50 (4%)	2
Constipation	2/50 (4%)	2
Vomiting/Nausea	1/50 (2%)	1
General disorders
Asthenia	4/50 (8%)	4
Renal and urinary disorders
Elevated creatinine	1/50 (2%)	1
Acute renal failure	2/50 (4%)	2
Other (Not Including Serious) Adverse Events
	Bortezomib and Dexamethasone
	Affected / at Risk (%)	# Events
Total	0/50 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.