Melphalan and Amifostine Followed By One or Two Autologous or Syngeneic Stem Cell Transplants and Maintenance Therapy in Treating Patients With Stage II-III Multiple Myeloma

Refractory Multiple Myeloma Clinical Trial

Official title:

A Multi-Center Phase III Study of Autologous Transplantation for Patients With Multiple Myeloma Comparing Melphalan 280 mg/m2 + Amifostine With Melphalan 200 mg/m2 + Amifostine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00217438
• Other study ID #: 2004.00
• Secondary ID: NCI-2009-01543
• Status: Completed
• Phase: Phase 3
• First received: September 20, 2005
• Last updated: August 4, 2015
• Start date: July 2005

Study information

• Verified date: August 2015
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Giving chemotherapy drugs, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. Giving chemotherapy with a peripheral stem cell transplant once or twice, using stem cells from the patient or an identical brother or sister, may allow more chemotherapy to be given so more cancer cells are killed. Giving maintenance therapy after a stem cell transplant may kill any cancer cells that remain. It is not yet known which dose of melphalan is more effective in treating multiple myeloma (MM).

PURPOSE: This randomized phase III trial is studying two different doses of melphalan to compare how well they work when given together with amifostine followed by one or two autologous or syngeneic stem cell transplants and maintenance therapy in treating patients with stage II-III MM

Description:

PRIMARY OBJECTIVES:

I. Compare the complete response (CR) and near CR rate in patients undergoing autologous stem cell transplant (ASCT) using melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

SECONDARY OBJECTIVES:

I. Compare toxicities between patients receiving amifostine and melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

INDUCTION THERAPY:

ARM I (HIGH DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine intravenously (IV) over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

ARM II (LOW DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

After completion of study treatment, patients are followed up every 3 months for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients who have MM undergoing autologous or syngeneic hematopoietic transplantation

• Patients must meet Salmon and Durie criteria for initial diagnosis of MM

• Transplant will be offered to patients with stage II or III MM

• Measurable disease, defined as serum monoclonal protein >= 0.2 g/dl or Bence Jones protein >= 200 mg/24 h

• Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2

• Life expectancy is not severely limited by concomitant illness

• Left ventricular ejection fraction >= 50%

• No uncontrolled arrhythmias or symptomatic cardiac disease

• Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO) >= 50%

• No symptomatic pulmonary disease

• Human immunodeficiency virus (HIV) negative

• Bilirubin < 2 mg/dl

• Serum glutamic pyruvate transaminase (SGPT) < 2.5 x normal

• Creatinine clearance >= 60 cc/min, estimated or measured

• Signed informed consent

Exclusion Criteria:

• Pregnant or lactating females

• Uncontrolled infection

• Planned tandem autologous/reduced intensity allograft

• Insufficient PBSC for an autologous transplant (< 3.0 x 10^6 CD34+ cells/kg total)

• Prior autologous transplant

• Non-secretory myeloma and patients who are in a complete response or near complete response after conventional therapy

• Patients unwilling to practice adequate forms of contraception if clinically indicated

• Male patients on study need to be consulted to use latex condoms, even if they have had a vasectomy, every time they have sex with a woman who is able to have children

• Patients with history of seizures

• Patients receiving antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage II Multiple Myeloma
• Stage III Multiple Myeloma

Intervention

Drug:
• melphalan
Given IV
• amifostine trihydrate
Given IV

Procedure:
• peripheral blood stem cell transplantation
Undergo PBSCT

Genetic:
• fluorescence in situ hybridization
Correlative study

Procedure:
• bone marrow ablation with stem cell support
Undergo transplant

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Rochester	Rochester	New York
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	VA Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CR and Near CR Rates	Per modified European Group for Blood and Marrow Transplant (EBMT) response criteria for definition of response in patients with multiple myeloma treated by high-dose therapy and stem cell transplantation: Complete Response (CR): Complete disappearance of all clinically measurable disease, complete response requires negative tests for monoclonal proteins in serum and urine by immunofixation, no monoclonal plasma cells in marrow specimen by flow cytometry and no evidence of progressive bone disease by skeletal survey. "Near" Complete Response (nCR): Less than 0.1 gram/dL monoclonal protein detectable in serum by standard protein electrophoresis and less than 50 mg monoclonal protein detectable in urine on 24 hour collection. Less than 5% monoclonal plasma cells detectable in bone marrow by immunohistochemistry. No evidence of progressive bone disease by skeletal survey.	Up to 120 days after transplant	No
Secondary	Relative Toxicities Between Melphalan 280 mg/m^2 or Melphalan 200 mg/m^2	Number of Grade 3-4 adverse events observed in each group from enrollment through the Day 80-120 evaluation. Grade 3-4 events are defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.	Up to day 56 after transplant	No