NCT00217438

Brief 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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
130

participants targeted

Target at P25-P50 for phase_3

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

September 20, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 22, 2005

Completed
7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
2 years until next milestone

Results Posted

Study results publicly available

September 19, 2014

Completed
Last Updated

August 21, 2015

Status Verified

August 1, 2015

Enrollment Period

7.3 years

First QC Date

September 20, 2005

Results QC Date

November 1, 2013

Last Update Submit

August 4, 2015

Conditions

Refractory Multiple MyelomaStage II Multiple MyelomaStage III Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Relative Toxicities Between Melphalan 280 mg/m^2 or Melphalan 200 mg/m^2

    Up to day 56 after transplant

Study Arms (2)

Arm I (high dose melphalan, amifostine trihydrate, transplant)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive amifostine IV over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2. AUTOLOGOUS OR SYNGENEIC 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.

Drug: melphalanDrug: amifostine trihydrateProcedure: peripheral blood stem cell transplantationGenetic: fluorescence in situ hybridizationProcedure: bone marrow ablation with stem cell support

Arm II (low dose melphalan, amifostine trihydrate, transplant)

ACTIVE COMPARATOR

INDUCTION THERAPY: Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose. AUTOLOGOUS OR SYNGENEIC 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.

Drug: melphalanDrug: amifostine trihydrateProcedure: peripheral blood stem cell transplantationGenetic: fluorescence in situ hybridizationProcedure: bone marrow ablation with stem cell support

Interventions

melphalanDRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Arm I (high dose melphalan, amifostine trihydrate, transplant)Arm II (low dose melphalan, amifostine trihydrate, transplant)
amifostine trihydrateDRUG

Given IV

Also known as: ethiofos, Ethyol, gammaphos, WR-2721
Arm I (high dose melphalan, amifostine trihydrate, transplant)Arm II (low dose melphalan, amifostine trihydrate, transplant)
peripheral blood stem cell transplantationPROCEDURE

Undergo PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Arm I (high dose melphalan, amifostine trihydrate, transplant)Arm II (low dose melphalan, amifostine trihydrate, transplant)
fluorescence in situ hybridizationGENETIC

Correlative study

Also known as: fluorescence in situ hybridization (FISH)
Arm I (high dose melphalan, amifostine trihydrate, transplant)Arm II (low dose melphalan, amifostine trihydrate, transplant)
bone marrow ablation with stem cell supportPROCEDURE

Undergo transplant

Arm I (high dose melphalan, amifostine trihydrate, transplant)Arm II (low dose melphalan, amifostine trihydrate, transplant)

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

MelphalanAmifostinePeripheral Blood Stem Cell TransplantationIn Situ Hybridization, Fluorescence

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsOrganothiophosphatesOrganophosphatesOrganophosphorus CompoundsOrganothiophosphorus CompoundsSulfur CompoundsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeIn Situ HybridizationStaining and LabelingHistocytological Preparation TechniquesCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisHistological TechniquesInvestigative TechniquesCytogenetic AnalysisGenetic TechniquesNucleic Acid Hybridization

Results Point of Contact

Title
Dr. William Bensinger
Organization
Fred Hutchinson Cancer Research Center
wbensing@fhcrc.org
206-667-4933

Study Officials

  • William Bensinger

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 20, 2005

First Posted

September 22, 2005

Study Start

July 1, 2005

Primary Completion

October 1, 2012

Last Updated

August 21, 2015

Results First Posted

September 19, 2014

Record last verified: 2015-08

Locations

US(4)