Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

FM 140 vs FM100 Study in Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00505895
First received: July 20, 2007
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

The goal of this clinical research study is to learn if there is a difference in transplant outcomes between two different doses of melphalan given in combination with fludarabine followed by transfusion of a related or unrelated volunteer donor's peripheral blood or bone marrow progenitor cells (allogeneic stem cell transplant) in patients with multiple myeloma. This study will also look at whether treatment with a antibody called rituximab against a specific type of lymphocyte (B cell) will reduce the risks of developing graft versus host disease after transplant. The safety of these treatments will also be compared.


Condition Intervention Phase
Multiple Myeloma
Drug: Melphalan
Drug: Fludarabine
Procedure: Stem Cell Infusion
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Fludarabine/Melphalan 140 VS. Fludarabine/Melphalan 100 Followed By Allogeneic Peripheral Blood Stem Cell or Bone Marrow Transplantation for Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants With Successful Engraftment at Day 100 [ Time Frame: Day 100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute Grade II-IV Graft Versus Host Disease (GVHD) [ Time Frame: GVHD grading weekly during first 100 days; Annual examinations for nine year study period ] [ Designated as safety issue: Yes ]
    Effects of Rituximab as measured by percentage of participants with Acute and Chronic Graft Versus Host Disease (GVHD) incidences after allogeneic transplantation. GVHD occurring anytime after day 90 post transplant was considered chronic GVHD; otherwise it was considered acute GVHD. Acute GVHD status defined as GVHD with maximum grade ≥2. Clinical grading of Acute GVHD (Thomas et al., New England Journal of Medicine (NEJM), 229:895, 1975): Grade 1 to 4.


Enrollment: 52
Study Start Date: January 2002
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine + Melphalan + Stem Cell Infusion

Fludarabine 30 mg/m^2 intravenous (IV) daily over 30 minutes for 4 Days (Beginning Day -4).

Melphalan 140 mg/m^2 IV over 20 minutes on Day -1. Stem Cell Infusion on Day 0. Rituximab 375 mg/m^2 IV infused starting on day -5.

Drug: Melphalan
Arm 1 = 140 mg/m^2 intravenous over 20 Minutes on Day -1; Arm 2 = 100 mg/m^2 intravenous over 20 Minutes on Day -1.
Other Name: Alkeran
Drug: Fludarabine
30 mg/m^2 intravenous daily over 30 Minutes for 4 Days (Beginning Day -4).
Other Names:
  • Fludara
  • Fludarabine Phosphate
Procedure: Stem Cell Infusion
Stem Cell Infusion on Day 0.
Other Names:
  • Allogeneic Peripheral Blood Stem Cell Transfusion
  • APBSCT
  • Bone Marrow Transplantation
  • BMT
Drug: Rituximab
375 mg/m^2 intravenous on Day -5, +2 +9 and +16.
Other Name: Rituxan
Experimental: Fludarabine + Lower-Dose Melphalan + Stem Cell Infusion

Fludarabine 30 mg/m^2 intravenous daily over 30 minutes for 4 Days (Beginning Day -4).

Lower-Dose Melphalan 100 mg/m^2 intravenous over 20 minutes on Day -1. Stem Cell Infusion on Day 0. Rituximab 375 mg/m^2 intravenous infused starting on day -5.

Drug: Melphalan
Arm 1 = 140 mg/m^2 intravenous over 20 Minutes on Day -1; Arm 2 = 100 mg/m^2 intravenous over 20 Minutes on Day -1.
Other Name: Alkeran
Drug: Fludarabine
30 mg/m^2 intravenous daily over 30 Minutes for 4 Days (Beginning Day -4).
Other Names:
  • Fludara
  • Fludarabine Phosphate
Procedure: Stem Cell Infusion
Stem Cell Infusion on Day 0.
Other Names:
  • Allogeneic Peripheral Blood Stem Cell Transfusion
  • APBSCT
  • Bone Marrow Transplantation
  • BMT
Drug: Rituximab
375 mg/m^2 intravenous on Day -5, +2 +9 and +16.
Other Name: Rituxan

Detailed Description:

Fludarabine is a chemotherapy drug that is used in various diseases. Melphalan is a chemotherapy drug that has been widely used in the treatment of multiple myeloma for many years.

Before beginning therapy, patients will have a complete work-up. This includes a bone marrow aspiration and biopsy, bone survey, blood tests, and tests to check the heart and lung function. All patients will receive tacrolimus and methotrexate to prevent graft-versus-host disease.

Patients in this study will be randomly picked (as in the toss of a coin) to be in one of two treatment groups. There is an equal chance that a patient will be in either group.

Patients in the first group will receive fludarabine through the vein every day for four days. On the fourth day, patients will receive a dose of melphalan through the vein over 20 minutes. On the following day, patients will receive the donor cells as an infusion through their catheter.

Patients in the second group will receive fludarabine through the vein every day for four days. Patients in this group will receive a lower dose of melphalan through the vein over 20 minutes. After the last dose of fludarabine, patients will receive the donor cells as an infusion through their catheter the next day.

If you have an unrelated or a mismatched donor, you will receive the drug ATG (Thymoglobulin) by vein over 6 hours on Days -3, -2, and -1 (the 3 days before the transplant), to prevent graft versus host disease (GVHD) and to help engraftment.

Patients in both group will be receiving the monoclonal antibody called rituximab weekly starting on the fifth day before the stem cell transplant for a total of 4 doses.

Patients will remain in the hospital for about 4-6 weeks and in Houston Medical Center area at least 100 days after transplantation.

Patients whose disease gets worse will be taken off study. These patients will continue to be followed for survival.

This is an investigational study. All of the drugs used in this study are commercially available. The FDA has approved melphalan for the treatment of myeloma. Fludarabine is not approved for the treatment of myeloma but has been used for years as a way to prepare patients for transplant. About 30 to 60 patients will take part in this study. About 45 patients will be enrolled at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with Multiple Myeloma in any of the following disease categories: a) Primary Refractory considered poor candidate for autologous transplant, b) Remission Consolidation in patients with Chromosome 13 abnormalities or plasma cell leukemia, c) All relapsing patients.
  2. Age up to 70 years.
  3. Related or unrelated donor who is HLA-compatible in at least 9/10 alleles (A,B, C, DRB1 and DQ) by molecular techniques.
  4. Zubrod Performance Score (PS)<2.
  5. Life expectancy is not severely limited by concomitant illness. Left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) >40%.
  6. Patient and donor or guardian willing and able to sign informed consent.

Exclusion Criteria:

1) Patients with active central nervous system (CNS) disease are ineligible for this study as documented by clinical symptoms and/or testing.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00505895

Locations
United States, Texas
UT MD . Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Muzaffar H. Qazilbash, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00505895     History of Changes
Other Study ID Numbers: ID01-518
Study First Received: July 20, 2007
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Multiple Myeloma
Fludarabine
Fludara
Fludarabine Phosphate
Melphalan
Alkeran
Stem Cell Infusion
Stem Cell Transfusion
SCT
Allogeneic Peripheral Blood Stem Cell Transfusion
APBSCT
Bone Marrow Transplantation
BMT
Rituxan
Rituximab
FM140
FM100

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
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Fludarabine
Fludarabine phosphate
Melphalan
Rituximab
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 24, 2014