Bortezomib and Thalidomide in Treating Patients With Newly Diagnosed Stage II or Stage III Multiple Myeloma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00287872
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 74
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with thalidomide works in treating patients with newly diagnosed stage II or stage III multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: bortezomib; Drug: thalidomide	Phase 2

Detailed Description

OBJECTIVES:

• Determine the antitumor efficacy of bortezomib and thalidomide in patients with newly diagnosed stage II or III multiple myeloma.

• Determine the incidence and severity of peripheral motor/sensory neuropathy in patients treated with this regimen.

• Assess the ability to mobilize and collect stem cells in patients who undergo future autologous peripheral stem cell transplantation.

• Determine the time to response in patients treated with this regimen.

• Assess the quality of life of patients treated with this regimen.

OUTLINE: This is an open-label study.

Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses. Patients who plan to undergo transplantation AND achieve ≥ 50% reduction in the tumor burden proceed to transplantation off study. Patients who do not undergo transplantation receive 2 additional courses of therapy beyond best response for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients who achieve at least a partial response after completion of treatment may receive maintenance therapy comprising bortezomib IV every 2 months and oral thalidomide* once daily OR twice every 2 months (i.e., the day before and the day of bortezomib administration) in the absence of disease progression or unacceptable toxicity.

NOTE: *For patients who had previously discontinued thalidomide, maintenance therapy may consist of bortezomib only.

Quality of life is assessed at baseline, at the beginning of each study course, and after completion of study treatment.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

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: VELCADE (Bortezomib) and Thalidomide in Newly Diagnosed Patients With Multiple Myeloma
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib and Thalidomide The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide.	Drug: bortezomib; Other Names: VELCADE ; Drug: thalidomide

Outcome Measures

Primary Outcome Measures

1. Clinical Response to Treatment [1-6 months]

   Clinical evaluations of disease response were determined with each cycle. Bone marrow biopsies were done at baseline and at study termination. Clinical responses were defined by the International Myeloma Working Group criteria: Stringent Complete Response (SCR), CR and normal free light chain ratio and no clonal cells in bone marrow; Complete Response (CR), Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; Very Good Partial Response (VGPR), Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; Partial Response (PR), ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. Objective response is defined as a best overall response of SCR, CR, VGPR, or PR.

Secondary Outcome Measures

1. Peripheral Motor and Sensory Neuropathy (Grade 2 and Higher) [1-6 months]

   Neuropathy was monitored using Total Neuropathy Score reduced (TNSr).

2. Mobilization of Stem Cells in Patients Proceeding to Autologous Peripheral Stem Transplantation [1-6 months]

3. The Time to Response [1-6 months]

4. Quality of Life [0-6 months]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Newly diagnosed Salmon-Durie stage II or III multiple myeloma

• Untreated disease OR patient underwent prior therapy for this cancer that lasted no more than 2 weeks

• Measurable paraprotein in serum or urine (serum free-lite assay measurement allowed)

• No evidence of cord compression requiring concurrent steroids

PATIENT CHARACTERISTICS:

• Creatinine clearance ≥ 30 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use 2 methods of contraception, including ≥ 1 highly effective method, 4 weeks before, during, and for ≥ 4 weeks after completion of study treatment

• No known HIV positivity

• No peripheral neuropathy ≥ grade 2

• No hypersensitivity to bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

• No prior bortezomib

• More than 28 days since prior regimens with a duration of > 1 week but ≤ 2 weeks

• No steroids within 14 days prior to study entry

• No concurrent corticosteroids except for the treatment of a nonmalignant condition

• May not exceed the equivalent dose of prednisone 10 mg/day

• No concurrent chemotherapy, immunotherapy, radiotherapy, or surgery

• No other concurrent investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ivan Borrello, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00287872
• Other Study ID Numbers: J0456 CDR0000450772; P30CA006973; JHOC-J0456; JHOC-04063003; MILLENNIUM-JHOC-J0456
• First Posted: Feb 7, 2006
• Last Update Posted: Mar 1, 2018
• Last Verified: Jun 1, 2014

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Bortezomib

Study Results

Participant Flow

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Period Title: Overall Study
STARTED	30
COMPLETED	30
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (9.9)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	24 80%
>=65 years	6 20%
Sex: Female, Male (Count of Participants)
Female	19 63.3%
Male	11 36.7%
Region of Enrollment (participants) [Number]
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Response to Treatment
Description	Clinical evaluations of disease response were determined with each cycle. Bone marrow biopsies were done at baseline and at study termination. Clinical responses were defined by the International Myeloma Working Group criteria: Stringent Complete Response (SCR), CR and normal free light chain ratio and no clonal cells in bone marrow; Complete Response (CR), Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; Very Good Partial Response (VGPR), Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; Partial Response (PR), ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. Objective response is defined as a best overall response of SCR, CR, VGPR, or PR.
Time Frame	1-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Measure Participants	27
Number (95% Confidence Interval) [percentage of participants]	81.5 271.7%

2. Secondary Outcome

Title	Peripheral Motor and Sensory Neuropathy (Grade 2 and Higher)
Description	Neuropathy was monitored using Total Neuropathy Score reduced (TNSr).
Time Frame	1-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Measure Participants	27
Number [participants]	19 63.3%

3. Secondary Outcome

Title	Mobilization of Stem Cells in Patients Proceeding to Autologous Peripheral Stem Transplantation
Time Frame	1-6 months

Outcome Measure Data

Analysis Population Description

Analysis not completed as the information was not relevant since no patients went on to transplant.

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Measure Participants	0

4. Secondary Outcome

Title	The Time to Response
Time Frame	1-6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Measure Participants	22
Median (95% Confidence Interval) [months]	2

5. Secondary Outcome

Title	Quality of Life
Time Frame	0-6 months

Outcome Measure Data

Analysis Population Description

Analysis not done on subject population.

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
Measure Participants	0

Adverse Events

Arm/Group Title	Bortezomib and Thalidomide
Arm/Group Description	The patients will receive Bortezomib on days 1, 4, 8 and 11 of each 21 day cycle in combination with daily oral Thalidomide. bortezomib thalidomide
All Cause Mortality
	Bortezomib and Thalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bortezomib and Thalidomide
	Affected / at Risk (%)	# Events
Total	10/30 (33.3%)
Gastrointestinal disorders
dehydration	2/30 (6.7%)	2
nausea & vomiting	2/30 (6.7%)	2
Infections and infestations
neutropenic fever	1/30 (3.3%)	1
pneumonia	3/30 (10%)	3
Metabolism and nutrition disorders
hyperkalemia	1/30 (3.3%)	1
Renal and urinary disorders
renal failure	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Bortezomib and Thalidomide
	Affected / at Risk (%)	# Events
Total	25/30 (83.3%)
Cardiac disorders
hypotension	6/30 (20%)	7
Gastrointestinal disorders
constipation	19/30 (63.3%)	40
diarrhoea	15/30 (50%)	29
General disorders
fatigue	22/30 (73.3%)	48
Nervous system disorders
peripheral neuropathy	25/30 (83.3%)	75

Limitations/Caveats

[Not Specified]

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.