Rituximab and Cyclophosphamide in Treating Patients With High Risk, Refractory, or Relapsed Multiple Myeloma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00258206
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 33.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with cyclophosphamide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with cyclophosphamide works in treating patients with high risk, refractory, or relapsed multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: rituximab; Drug: cyclophosphamide	Phase 2

Detailed Description

OBJECTIVES:

• Determine the effect of rituximab and high-dose cyclophosphamide on the growth of myeloma stem cells in patients with high-risk, refractory, or relapsed multiple myeloma.

OUTLINE: Patients receive rituximab IV on days -10 and -7; once weekly for 4 weeks (after completion of high-dose cyclophosphamide); and then once in months 3, 6, 9, and 12. Patients also receive high-dose cyclophosphamide on days -3 to 0.

PROJECTED ACCRUAL: Not specified.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of High Dose Cyclophosphamide and Rituximab in Multiple Myeloma
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Sep 7, 2007
• Actual Study Completion Date: Sep 7, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rituximab + cyclophosphamide Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12	Biological: rituximab; Other Names: Rituxan ; Drug: cyclophosphamide; Other Names: Cytoxan

Outcome Measures

Primary Outcome Measures

1. Event-free Survival [1 year]

   Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse)

2. Safety of Maintenance Rituximab Following High Dose Cyclophosphamide [2, 3, 6, 9, and 12 months]

Secondary Outcome Measures

1. Safety and Toxicity [2, 3, 6, 9, and 12 months]

2. Complete Response (CR) Rate and Partial Response (PR) Rate [1 year]

3. Effect of Rituximab by Clonogenic Growth of Multiple Myeloma (MM) Progenitors and the Mechanisms by Which MM Stem Cells Are Inhibited [2, 3, 6, 9, and 12 months]

4. Overall Survival [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma, meeting 1 of the following criteria:

• High-risk disease in first remission, as defined by the following:

• Beta-2 microglobulin > 5.0 mg/dL

• Chromosome 13 deletion

• Primary refractory disease

• Relapsed disease after achieving a response to prior chemotherapy

• The following diagnoses are not allowed:

• POEMS syndrome

• Plasma cell leukemia

• Amyloidosis

• Nonsecretory myeloma

• No evidence of spinal cord compression

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception

• HIV negative

• Has good organ function

• Is in good physical condition

• No active infection requiring antibiotics

• No other malignancy within the past 2 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No persistently detectable donor cells after prior allogeneic stem cell transplantation

• No prior rituximab

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• At least 28 days since prior therapy

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

• Study Chair: Carol A. Huff, 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: NCT00258206
• Other Study ID Numbers: J0478 CDR0000441169; P30CA006973; JHOC-J0478
• First Posted: Nov 24, 2005
• Last Update Posted: Dec 6, 2017
• Last Verified: Nov 1, 2017

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

Study Results

Participant Flow

Arm/Group Title	Rituximab + Cyclophosphamide
Arm/Group Description	Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12
Period Title: Overall Study
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Rituximab + Cyclophosphamide
Arm/Group Description	Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 81%
>=65 years	4 19%
Sex: Female, Male (Count of Participants)
Female	14 66.7%
Male	7 33.3%
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	6 28.6%
White	15 71.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival
Description	Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab + Cyclophosphamide
Arm/Group Description	Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12
Measure Participants	21
Number [percentage of participants]	29 138.1%

2. Primary Outcome

Title	Safety of Maintenance Rituximab Following High Dose Cyclophosphamide
Time Frame	2, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Safety and Toxicity
Time Frame	2, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Complete Response (CR) Rate and Partial Response (PR) Rate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Effect of Rituximab by Clonogenic Growth of Multiple Myeloma (MM) Progenitors and the Mechanisms by Which MM Stem Cells Are Inhibited
Time Frame	2, 3, 6, 9, and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Rituximab + Cyclophosphamide
Arm/Group Description	Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12
All Cause Mortality
	Rituximab + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rituximab + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab + Cyclophosphamide
	Affected / at Risk (%)	# Events
Total	0/21 (0%)

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.