Adjuvant Bortezomib Maintenance Therapy After Autologous Peripheral Stem Cell Transplantation in Treating Patients With Intermediate or Advanced Multiple Myeloma

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00084747
• Collaborator: Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 103
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving bortezomib as maintenance therapy after autologous stem cell transplantation may kill more cancer cells and prolong remission.

PURPOSE: This phase I/II trial is studying the side effects and best dose of adjuvant bortezomib as maintenance therapy and to see how well it works in treating patients who have undergone stem cell transplantation for intermediate or advanced multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

• Determine response rate, as defined by resolution of bone marrow plasmacytosis and monoclonal paraproteinemia, in the first year after autologous peripheral blood stem cell transplantation in patients with intermediate or advanced multiple myeloma treated with adjuvant bortezomib.

• Compare progression-free survival of patients treated with adjuvant bortezomib with historical controls treated with autologous transplantation alone.

• Determine the toxicity of this drug in these patients (phase I).

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive bortezomib IV on days 1, 8, and 15. Treatment repeats every 28 days for 8 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 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study within 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Autologous Peripheral Blood Progenitor Cell Transplantation With VELCADE Maintenance as Treatment for Intermediate- and Advanced-Stage Multiple Myeloma
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bortezomib	Drug: bortezomib

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [signed consent to progression or end of trial. Up to 5 years.]

   Disease Progression: The day when bone marrow recurrence and/or new lytic bone marrow lesions on radiograph and/or progressive M-component paraprotein (~ 25% increase) were detected. Paraprotein progression will be confirmed labs on the consecutive month.

Secondary Outcome Measures

1. Overall Survival [up to 5 years from time of consent]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of intermediate or advanced multiple myeloma meeting criteria for at least 1 2 following:

• Intermediate- to high-M-component production rates (immunoglobulin [Ig]G > 5 g/dL or immunoglobulin A (IgA) > 3 g/dL or urine M component > 4 g/24 hours)

• More than one osteolytic bone lesion or radiographic evidence of diffuse osteoporosis

• β-2 microglobulin > 3

• Nonsecretory myeloma if bone marrow plasmacytosis is greater than 30%

• Must have undergone autologous peripheral blood stem cell transplantation within the past 3-4 months

• Age 18 to 69 years old

• Absolute neutrophil count ≥ 1,000/mm^3

• Platelet count ≥ 30,000/mm^3

• serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) ≤ 300 IU

• Bilirubin ≤ 2 mg/dL

• Creatinine ≤ 2.0 mg/dL

• Creatinine clearance ≥ 30 mL/min

• Negative pregnancy test

• Fertile patients must use effective contraception

Exclusion Criteria:

• concurrent major cardiac disease that would preclude study participation

• concurrent major pulmonary disease that would preclude study participation

• pregnant or nursing

• peripheral neuropathy ≥ grade 2

• history of hypersensitivity to bortezomib, boron, or mannitol

• concurrent major gastrointestinal or bladder disease that would preclude study participation

• concurrent major neurologic or psychiatric disease that would preclude study participation

• dementia or significantly altered mental status that would preclude giving informed consent

• prior interferon post-transplantation

• prior thalidomide post-transplantation

• prior chemotherapy post-transplantation

• prior radiotherapy post-transplantation

• prior investigational therapy post-transplantation

• prior bortezomib

• prior therapy for myeloma post-transplantation

• other concurrent anti-myeloma therapy

• other concurrent investigational therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Gary J. Schiller, MD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00084747
• Other Study ID Numbers: CDR0000365583; UCLA-0306106; MILLENNIUM-MM2003
• First Posted: Jun 11, 2004
• Last Update Posted: Aug 17, 2020
• Last Verified: Feb 1, 2016

• Keywords provided by Jonsson Comprehensive Cancer Center: stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Bortezomib
Arm/Group Description	bortezomib administration beginning 3-4 month after the day of transplantation after resolution of bone marrow transplant toxicities
Period Title: Overall Study
STARTED	30
COMPLETED	17
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Bortezomib
Arm/Group Description	bortezomib administration beginning 3-4 month after the day of transplantation after resolution of bone marrow transplant toxicities
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 90%
>=65 years	3 10%
Sex: Female, Male (Count of Participants)
Female	16 53.3%
Male	14 46.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Disease Progression: The day when bone marrow recurrence and/or new lytic bone marrow lesions on radiograph and/or progressive M-component paraprotein (~ 25% increase) were detected. Paraprotein progression will be confirmed labs on the consecutive month.
Time Frame	signed consent to progression or end of trial. Up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib
Arm/Group Description	autologous peripheral blood progenitor cell transplantation with bortezomib maintenance as treatment for intermediate-and advanced-stage multiple myeloma
Measure Participants	30
Median (Full Range) [months]	29

2. Secondary Outcome

Title	Overall Survival
Time Frame	up to 5 years from time of consent

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib
Arm/Group Description	bortezomib
Measure Participants	30
Median (Full Range) [months]	55

Adverse Events

Time Frame	Adverse event information was collected from the time subject signed consent until 30 days post last treatment up to 2 years.
Arm/Group Title	Bortezomib
Arm/Group Description	bortezomib administration beginning 3-4 month after the day of transplantation after resolution of bone marrow transplant toxicities
All Cause Mortality
	Bortezomib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bortezomib
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
General disorders
Nausea/Dehydration	1/30 (3.3%)	2
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/30 (3.3%)	2
Other (Not Including Serious) Adverse Events
	Bortezomib
	Affected / at Risk (%)	# Events
Total	19/30 (63.3%)
Gastrointestinal disorders
Dyspepsia	1/30 (3.3%)	1
Diarrhea	7/30 (23.3%)	7
Constipation	3/30 (10%)	3
General disorders
Fatigue	19/30 (63.3%)	19
Anorexia	1/30 (3.3%)	1
nausea/vomiting	9/30 (30%)	9
Neuropathy	11/30 (36.7%)	11
Pain	17/30 (56.7%)	17
Peripheral Edema	1/30 (3.3%)	1
Rash	2/30 (6.7%)	2
Neutrophils	6/30 (20%)	6
Platelets	10/30 (33.3%)	10
Right extremity swelling, with no DVT	1/30 (3.3%)	1
Immune system disorders
Herpes Zoster Reactivation	7/30 (23.3%)	7
Infections and infestations
Fever	1/30 (3.3%)	1
Cough	4/30 (13.3%)	4
Upper Respiratory Infection	2/30 (6.7%)	2
Transaminits 2/2 Hep A from contaminated food	1/30 (3.3%)	1

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.