Autologous Transplant for Multiple Myeloma

Autologous Transplantation for Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Procedure: Stem Cell Transplant; Drug: Cyclophosphamide + Mesna; Drug: Melphalan; Biological: Granulocyte-colony stimulating factor

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.

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Chemotherapy and Transplant Treatment; 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; 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.; Other Names: Bone Marrow Transplant; Drug: Cyclophosphamide + Mesna; Cyclophosphamide: 4mg/m^2 + Mesna. Mesna is used to reduce the undesired side effects of certain chemotherapy drugs.; Other Names: Cytoxan; Drug: Melphalan; Administered intravenously 200 mg/m^2; Other Names: Alkeran; Biological: Granulocyte-colony stimulating factor; Administered intravenously 10 ug/kg/day pretransplant then 5 ug/kg/day post-transplant.; Other Names: G-CSF

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2004
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 7, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: chemotherapy; stem cell transplantation; autologous; multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Adjuvants, Immunologic; Cyclophosphamide; Lenograstim; Melphalan
• Other Study ID Numbers: 2004LS001; MT2003-13 (Other Identifier: Blood and Marrow Transplantation Program); 0312M54569 (Other Identifier: IRB, University of Minnesota)