Multiple Myeloma
Conditions
Keywords
stem cell transplantation, chemotherapy, multiple myeloma, autologous
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.
Interventions
PROCEDUREStem 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.
DRUGCyclophosphamide + Mesna
Cyclophosphamide: 4mg/m\^2 + Mesna. Mesna is used to reduce the undesired side effects of certain chemotherapy drugs.
DRUGMelphalan
Administered intravenously 200 mg/m\^2
BIOLOGICALGranulocyte-colony stimulating factor
Administered intravenously 10 ug/kg/day pretransplant then 5 ug/kg/day post-transplant.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving a Complete Response | 100 Days 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival | 1 year | 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. |
| 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. |
| 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. |
| 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 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. |
| 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 |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 363 |
| Total | 363 |
Baseline characteristics
| Characteristic | Chemotherapy and Transplant Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 106 Participants |
| Age, Categorical Between 18 and 65 years | 257 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 313 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 42 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants |
| Race (NIH/OMB) White | 304 Participants |
| Region of Enrollment United States | 363 participants |
| Sex: Female, Male Female | 166 Participants |
| Sex: Female, Male Male | 197 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 62 / 363 |
| other Total, other adverse events | 194 / 363 |
| serious Total, serious adverse events | 2 / 363 |
Outcome results
Primary
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.
Time frame: 100 Days post transplant
Population: 173 participants were not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants Achieving a Complete Response | 51 Participants |
Primary
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.
Time frame: 6 months post transplant
Population: 54 participants were not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants Achieving a Complete Response | 99 Participants |
Primary
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.
Time frame: 12 months post transplant
Population: 55 participants were not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants Achieving a Complete Response | 123 Participants |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Count of Participants Experiencing Transplant Related Mortality | 3 Participants |
Secondary
Dropout Rate From Maintenance Therapy
Time frame: Post transplant phase
Population: Data not available for this outcome at our center, maintenance treatment data for participants is not available as the EPIC system was not in place when this study was conducted and participants moved to different clinics so follow-up details were no available.
Secondary
Duration of Maintenance Treatment
Time frame: During study
Population: Data not available for this outcome at our center, maintenance treatment data for participants is not available as the EPIC system was not in place when this study was conducted and participants moved to different clinics so follow-up details were no available.
Secondary
Number of Participants Experiencing Incidence of Relapse
The return of disease after its apparent recovery/cessation.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants Experiencing Incidence of Relapse | 69 Participants |
Secondary
Number of Participants With Absolute Neutrophil Recovery
Hematologic recovery is defined by absolute neutrophil count (ANC) \>2500/μl and platelets \> 100,000/μl
Time frame: Day 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Absolute Neutrophil Recovery | 363 Participants |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Disease Progression | 34 Participants |
Secondary
Number of Participants With Infections
Occurrence of infections in the patients by the first 100 days of transplant
Time frame: By first 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Infections | 68 Participants |
Secondary
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.
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Overall Survival | 301 Participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Overall Survival | 328 Participants |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Overall Survival | 349 Participants |
Secondary
Number of Participants With Toxicities
Occurrence of toxicities by first 100 days of transplant
Time frame: By first 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Participants With Toxicities | 68 Participants |
Secondary
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.
Time frame: 36 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Chemotherapy and Transplant Treatment | Number of Patients With Extended Disease-free Survival | 164 Participants |
Secondary
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
Time frame: 12 months post transplant
Population: Data was not available on everyone for this endpoint so could only evaluable for 308 out of 363 patients due to data for participants is not available as the EPIC system was not in place when this study was conducted and participants moved to different clinics we do not have follow-up details.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chemotherapy and Transplant Treatment | Time to Attainment of CR | 4.6 months | Standard Deviation 1.5 |
Secondary
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
Time frame: 12 months post transplant
Population: 55 patients were not evaluable Data was not available on everyone for this endpoint so could not evaluate all 363 patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chemotherapy and Transplant Treatment | Time to Attainment of CR+PR | 4.3 months | Standard Deviation 1.5 |
Secondary
Time to Progression
Mean number of days among patients progressing
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chemotherapy and Transplant Treatment | Time to Progression | 159.4 Days | Standard Deviation 109.8 |
Secondary
Time to Relapse
Mean number of days among patients relapsing
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chemotherapy and Transplant Treatment | Time to Relapse | 182.9 Days | Standard Deviation 113.5 |