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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
First received: November 22, 2005
Last updated: June 10, 2015
Last verified: June 2015

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Biological: rituximab
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of High Dose Cyclophosphamide and Rituximab in Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Event-free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse)

  • Safety of Maintenance Rituximab Following High Dose Cyclophosphamide [ Time Frame: 2, 3, 6, 9, and 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety and Toxicity [ Time Frame: 2, 3, 6, 9, and 12 months ] [ Designated as safety issue: Yes ]
  • Complete Response (CR) Rate and Partial Response (PR) Rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: December 2004
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Rituxan
Drug: cyclophosphamide
Other Name: Cytoxan

Detailed Description:


  • 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.



Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • Over 18

Performance status

  • Not specified

Life expectancy

  • Not specified


  • Not specified


  • Not specified


  • Not specified


  • 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


Biologic therapy

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


  • See Disease Characteristics

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • At least 28 days since prior therapy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00258206

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Carol A. Huff, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00258206     History of Changes
Other Study ID Numbers: J0478 CDR0000441169, P30CA006973, JHOC-J0478
Study First Received: November 22, 2005
Results First Received: May 28, 2015
Last Updated: June 10, 2015
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on December 01, 2015