Trial Outcomes & Findings for 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 (NCT NCT00217438)

Last Updated: 2015-08-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

130 participants

Primary outcome timeframe

Up to 120 days after transplant

Results posted on

2015-08-21

Participant Flow

This trial opened for enrollment September 2005 and completed enrollment in June 2012. Patients were enrolled at 4 centers: University of Washington, Seattle, WA; Veteran's Administration Puget Sound Healthcare Administration, Seattle, WA; Cedars Sinai Medical Center, Los Angeles, CA; and James Wilmot Cancer Center in Rochester, NY.

Participant milestones

Participant milestones
Measure	Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant) 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.	Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant) 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.
Overall Study STARTED	66	64
Overall Study COMPLETED	66	63
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant) n=66 Participants 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.	Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant) n=64 Participants 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.	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	57 Participants n=93 Participants	55 Participants n=4 Participants	112 Participants n=27 Participants
Age, Categorical >=65 years	9 Participants n=93 Participants	9 Participants n=4 Participants	18 Participants n=27 Participants
Sex: Female, Male Female	23 Participants n=93 Participants	23 Participants n=4 Participants	46 Participants n=27 Participants
Sex: Female, Male Male	43 Participants n=93 Participants	41 Participants n=4 Participants	84 Participants n=27 Participants
Region of Enrollment United States	66 participants n=93 Participants	64 participants n=4 Participants	130 participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 120 days after transplant

Population: Per protocol, patients who completed the day 80-120 evaluation assessments.

Outcome measures

Outcome measures
Measure	Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant) n=66 Participants 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.	Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant) n=63 Participants 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.
CR and Near CR Rates	39 percentage of participants	22 percentage of participants

SECONDARY outcome

Timeframe: Up to day 56 after transplant

Population: Patients who were treated per protocol.

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.

Outcome measures

Outcome measures
Measure	Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant) n=66 Participants 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.	Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant) n=64 Participants 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.
Relative Toxicities Between Melphalan 280 mg/m^2 or Melphalan 200 mg/m^2	20 Grade 3-4 adverse events	10 Grade 3-4 adverse events

Adverse Events

Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant)

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Arm I (High Dose Melphalan, Amifostine Trihydrate, Transplant) n=66 participants at risk 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.	Arm II (Low Dose Melphalan, Amifostine Trihydrate, Transplant) n=64 participants at risk 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.
Gastrointestinal disorders Mucositis-Grade 3 or higher	10.6% 7/66 • Number of events 7	4.7% 3/64 • Number of events 3
Gastrointestinal disorders Diarrhea	10.6% 7/66 • Number of events 7	4.7% 3/64 • Number of events 3
Cardiac disorders Atrial fibrillation	0.00% 0/66	1.6% 1/64 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.5% 1/66 • Number of events 1	0.00% 0/64
Nervous system disorders Neutropenic fever	1.5% 1/66 • Number of events 1	0.00% 0/64
Gastrointestinal disorders Nausea/Vomiting	10.6% 7/66 • Number of events 7	3.1% 2/64 • Number of events 2
Gastrointestinal disorders Dehydration	0.00% 0/66	1.6% 1/64 • Number of events 1
Gastrointestinal disorders Anorexia	1.5% 1/66 • Number of events 1	0.00% 0/64
Gastrointestinal disorders Graft versus host disease of the gut	1.5% 1/66 • Number of events 1	0.00% 0/64

Additional Information

Dr. William Bensinger

Fred Hutchinson Cancer Research Center

Phone: 206-667-4933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 30 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication. In the event the sponsor decides a patent application should be filed, the embargo may extend up to an additional 60 days or until a patent application is filed.
Publication restrictions are in place

Restriction type: OTHER