Autologous Transplant for Multiple Myeloma

Study Overview
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Brief Summary
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This is a study of a regimen of melphalan and autologous stem cells for patients with multiple myeloma. We hypothesize that this particular regimen will improve the survival of these patients.

Detailed Description
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Before starting treatment in this study, the bone marrow transplant (BMT) doctor will check the subject's general health. Subjects will have the following tests and evaluations to find out if they can participate:--Medical history and physical examination, including height and weight.--Blood tests (approximately 4 - 5 tablespoons) --Urine tests--Chest x-ray--Electrocardiogram (ECG or EKG)--Heart Scan (MUGA)--Pulmonary Function Test (PFT)--Bone marrow biopsies and aspirates. --If Female subjects of child-bearing age will have a serum pregnancy test performed. After eligible patients have been completely staged and exercised consent, they may undergo one cycle of chemotherapy (cyclophosphamide and Mesna) and growth factor (G-CSF) to effect cytoreduction and mobilization of PBSC for collection. All patients will receive high-dose melphalan followed by an autologous stem cell transplant (SCT). Blood tests will be performed frequently to evaluate the subject's response to treatment and possible side effects of treatment. If necessary, platelet and red cell transfusions will be given to maintain adequate levels and antibiotics will be given to treat or prevent infection. Subjects may also require intravenous nutritional support and pain medications during or after transplantation. The study coordinators will collect health information over three years. They will collect information every week for 100 days, then at 6 months, 1 year, 2 years, and 3 years.

Official Title
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Autologous Transplantation for Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Procedure: Stem Cell Transplant
* Drug: Cyclophosphamide + Mesna
* Drug: Melphalan
* Biological: Granulocyte-colony stimulating factor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients meeting the Durie and Salmon criteria for initial diagnosis of multiple myeloma, requiring therapy and meeting one of the following: After initial therapy in either first complete or partial remission or no objective response After achieving initial response and later disease progression, patient will be eligible after subsequent therapy upon achievement of either complete or partial response Is not eligible or has refused any protocols of higher priority 18 - 75 years of age Adequate organ function defined as: Hematologic: hemoglobin ≥ 8 gm/dl (untransfused), white blood cells (WBC) ≥ 3000/μl, absolute neutrophil count (ANC) ≥ 1500/μl, platelets ≥ 100,000/μl (untransfused) Cardiac: no active ischemia, left ventricular ejection fraction > 45% by MUGA scan Hepatic: bilirubin < 2.0 mg/dl, ALT < 3x the upper limit of normal Pulmonary: FEV1-Forced Expiratory Volume in One Second AND Forced vital capacity (FVC) >50% predicted and Carbon Monoxide Diffusing Capacity (DLCO) (corrected) > 50% predicted Performance status: Karnofsky performance of > 80%. Free of active uncontrolled infection at the time of study entry. At time of study enrollment > 4 weeks from prior myelosuppressive chemotherapy; and > 6 weeks from prior nitrosoureas. Patients must exercise informed voluntary consent and sign a consent form approved by the University of Minnesota IRB: Human Subjects Committee. Exclusion Criteria: Patients will be ineligible if they have advanced myeloma refractory and unresponsive to salvage chemotherapy regimens. Female patients who are pregnant (positive b-HCG) or breastfeeding will be excluded from study entry. In addition fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment, particularly after thalidomide will also be excluded from study entry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy and Transplant Treatment<br>Patients receiving peripheral blood stem cell mobilization, chemotherapy (cyclophosphamide + Mesna, growth factor (Granulocyte-colony stimulating factor) and autologous Peripheral Blood Stem Cell transplant with high dose melphalan (200 mg/m^2). Post-transplant maintenance therapy is then prescribed if appropriate. | Procedure: Stem Cell Transplant<br>* As part of the stem cell transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.<br>* Other names: Bone Marrow Transplant;Drug: Cyclophosphamide + Mesna<br>* Cyclophosphamide: 4mg/m^2 + Mesna. Mesna is used to reduce the undesired side effects of certain chemotherapy drugs.<br>* Other names: Cytoxan;Drug: Melphalan<br>* Administered intravenously 200 mg/m^2<br>* Other names: Alkeran;Biological: Granulocyte-colony stimulating factor<br>* Administered intravenously 10 ug/kg/day pretransplant then 5 ug/kg/day post-transplant.<br>* Other names: G-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving a Complete Response | Myeloma Response Definitions - Using International Uniform Response Criteria: Stringent Complete Response (sCR)requires, plus CR: Normal free light chain ratio Absence of clonal cells in bone marrow Complete Response (CR): Absence of the original monoclonal paraprotein <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas. | 100 Days post transplant | 
| Number of Participants Achieving a Complete Response | Myeloma Response Definitions - Using International Uniform Response Criteria: Stringent Complete Response (sCR)requires, plus CR: Normal free light chain ratio Absence of clonal cells in bone marrow Complete Response (CR): Absence of the original monoclonal paraprotein <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas. | 6 months post transplant | 
| Number of Participants Achieving a Complete Response | Myeloma Response Definitions - Using International Uniform Response Criteria: Stringent Complete Response (sCR)requires, plus CR: Normal free light chain ratio Absence of clonal cells in bone marrow Complete Response (CR): Absence of the original monoclonal paraprotein <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas. | 12 months post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Extended Disease-free Survival | Extended disease free survival will be defined as percentage of patients surviving more than 36 months without relapse or disease progression. | 36 Months | 
| Number of Participants With Overall Survival | The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. | 1 year | 
| Number of Participants With Overall Survival | The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. | 2 years | 
| Number of Participants With Overall Survival | The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. | 3 years | 
| Count of Participants Experiencing Transplant Related Mortality | In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation. | 1 year | 
| Number of Participants Experiencing Incidence of Relapse | The return of disease after its apparent recovery/cessation. | 1 year | 
| Number of Participants With Disease Progression | Myeloma Response Definitions - Using International Uniform Response Criteria: Progressive Disease (PD) For patients not in CR or sCR, progressive disease requires one or more of the following: >25% increase in the level of the serum monoclonal paraprotein, which must also be an absolute increase of at least 0.5 g/dL. >25% increase in 24-hour urine protein electrophoresis, which must also be an absolute increase of at least 200 mg/24 hours. Absolute increase in the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dl), only in patients without measurable paraprotein in the serum and urine. >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%. Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. | 1 year | 
| Time to Progression | Mean number of days among patients progressing | 1 year | 
| Time to Relapse | Mean number of days among patients relapsing | 1 year | 
| Number of Participants With Absolute Neutrophil Recovery | Hematologic recovery is defined by absolute neutrophil count (ANC) >2500/μl and platelets > 100,000/μl | Day 42 | 
| Time to Attainment of CR | Mean (STD) among patients achieving complete remission (CR) Myeloma Response Definitions - Using International Uniform Response Criteria: Complete Response (CR): Absence of the original monoclonal paraprotein <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas | 12 months post transplant | 
| Time to Attainment of CR+PR | Mean (STD) among patients achieving complete remission (CR) and partial remission (PR) Myeloma Response Definitions - Using International Uniform Response Criteria: Complete Response (CR): Absence of the original monoclonal paraprotein <5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy No increase in size or number of lytic bone lesions Disappearance of soft tissue plasmacytomas. Partial Response (PR): Greater than or equal to 50% reduction in the level of the serum monoclonal paraprotein and/or reduction in 24 hour urinary monoclonal paraprotein either by greater than or equal to 90% or to <200 mg/24 hours in light chain disease. If the only measurable non-bone marrow parameter is FLC, greater than or equal to 50% reduction in the difference between involved and uninvolved FLC levels or a 50% decrease in level | 12 months post transplant | 
| Duration of Maintenance Treatment |  | During study | 
| Dropout Rate From Maintenance Therapy |  | Post transplant phase | 
| Number of Participants With Toxicities | Occurrence of toxicities by first 100 days of transplant | By first 100 days | 
| Number of Participants With Infections | Occurrence of infections in the patients by the first 100 days of transplant | By first 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cell transplantation, chemotherapy, multiple myeloma, autologous