Autologous Transplant for Multiple Myeloma

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Procedure: Stem Cell Transplant
Drug: Cyclophosphamide + Mesna
Drug: Melphalan
Biological: Granulocyte-colony stimulating factor

Registration Number: NCT00177047

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 363

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chemotherapy and Transplant Treatment	Cyclophosphamide + Mesna	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.
Chemotherapy and Transplant Treatment	Stem Cell Transplant	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.
Chemotherapy and Transplant Treatment	Granulocyte-colony stimulating factor	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.
Chemotherapy and Transplant Treatment	Melphalan	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Achieving a Complete Response	12 months post transplant	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.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Extended Disease-free Survival	36 Months	Extended disease free survival will be defined as percentage of patients surviving more than 36 months without relapse or disease progression.
Number of Participants With Overall Survival	3 years	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.
Number of Participants With Disease Progression	1 year	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.
Count of Participants Experiencing Transplant Related Mortality	1 year	In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Number of Participants Experiencing Incidence of Relapse	1 year	The return of disease after its apparent recovery/cessation.
Time to Progression	1 year	Mean number of days among patients progressing
Time to Relapse	1 year	Mean number of days among patients relapsing
Number of Participants With Absolute Neutrophil Recovery	Day 42	Hematologic recovery is defined by absolute neutrophil count (ANC) \>2500/μl and platelets \> 100,000/μl
Time to Attainment of CR	12 months post transplant	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
Time to Attainment of CR+PR	12 months post transplant	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
Duration of Maintenance Treatment	During study
Dropout Rate From Maintenance Therapy	Post transplant phase
Number of Participants With Toxicities	By first 100 days	Occurrence of toxicities by first 100 days of transplant
Number of Participants With Infections	By first 100 days	Occurrence of infections in the patients by the first 100 days of transplant