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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-01543 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| melphalan | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William Bensinger | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States | ||
| University of Rochester |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| amifostine trihydrate | Drug | Given IV |
|
|
| peripheral blood stem cell transplantation | Procedure | Undergo PBSCT |
|
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| fluorescence in situ hybridization | Genetic | Correlative study |
|
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| bone marrow ablation with stem cell support | Procedure | Undergo transplant |
|
| Rochester |
| New York |
| 14642 |
| United States |
| VA Puget Sound Health Care System | Seattle | Washington | 98101 | United States |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| FG001 | 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. |
| COMPLETED |
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| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Per protocol, patients who completed the day 80-120 evaluation assessments. | Posted | Number | percentage of participants | Up to 120 days after transplant |
|
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| |||||||||||||||||||||||||||||
| 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. | Patients who were treated per protocol. | Posted | Number | Grade 3-4 adverse events | Up to day 56 after transplant |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 66 | 14 | 66 | ||
| EG001 | 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. | 0 | 64 | 7 | 64 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mucositis-Grade 3 or higher | Gastrointestinal disorders |
| |||
| Diarrhea | Gastrointestinal disorders | Mucositis recorded separately. |
| ||
| Atrial fibrillation | Cardiac disorders |
| |||
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders |
| |||
| Neutropenic fever | Nervous system disorders |
| |||
| Nausea/Vomiting | Gastrointestinal disorders | Mucositis recorded separately |
| ||
| Dehydration | Gastrointestinal disorders |
| |||
| Anorexia | Gastrointestinal disorders |
| |||
| Graft versus host disease of the gut | Gastrointestinal disorders |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. William Bensinger | Fred Hutchinson Cancer Research Center | 206-667-4933 | wbensing@fhcrc.org |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D008558 | Melphalan |
| D004999 | Amifostine |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D017404 | In Situ Hybridization, Fluorescence |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D063086 | Organothiophosphates |
| D010755 | Organophosphates |
| D009943 | Organophosphorus Compounds |
| D009946 | Organothiophosphorus Compounds |
| D013457 | Sulfur Compounds |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D017403 | In Situ Hybridization |
| D013194 | Staining and Labeling |
| D016591 | Histocytological Preparation Techniques |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D008919 | Investigative Techniques |
| D020732 | Cytogenetic Analysis |
| D005821 | Genetic Techniques |
| D009693 | Nucleic Acid Hybridization |
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| >=65 years |
|
| Male |
|
|
|