Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, High Risk, Intermediate Risk, Symptomatic
Brief summary
In this phase I trial, patients with multiple myeloma will receive standard high dose melphalan with autologous stem cell rescue. In addition the pre-transplant conditioning will include targeted total marrow irradiation (TMI). This conventional 3+3 phase I trial will increase the dose of TMI until the maximum tolerated dose (MTD) is reached. Initial patients enrolled will receive the lowest possible dose of 3Gy. Maximum dose will be 12Gy.
Detailed description
To establish the maximal tolerated dose of total marrow irradiation which can be added to high dose melphalan conditioning in patients with multiple myeloma undergoing autologous stem cell transplant.
Interventions
RADIATIONTotal Marrow Irradiation
Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy.
PROCEDUREAutologous Transplant
Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue.
DRUGMelphalan
Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning therapy prior to transplant.
Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC \> 1000/mm\^3 over period of 3 days.
Sponsors
University of Illinois at Chicago
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
1. Patients meeting criteria for symptomatic myeloma 2. Patients must be high or intermediate risk of disease progression as defined by having one of the following criteria: 2.1 ISS stage 2 or 3 disease 2.2 Abnormal metaphase cytogenetics 2.3 Presence of FISH abnormalities aside from hyperdiploidy 3. Patients who have received at least 2 cycles of systemic treatment of any kind in the preceding 12 months 4. Patient age 18-75 years at time of enrollment 5. Karnofsky performance status of ≥70 6. Cardiac function: LVEF \>40% 7. Hepatic: Bilirubin \<2x upper limit of normal and ALT and AST \< 2.5x the upper limit of normal 8. Renal: Creatinine clearance of ≥30mL/min, estimated or calculated 9. Pulmonary: DLCO, FEV1, FVC \>50% of predicted (after correction for hemoglobin)
Exclusion criteria
1. Patients with diagnosis of plasma cell leukemia 2. Patients with myeloma who have had any disease progression prior to enrollment 3. Patients with truly non secretory myeloma (patients with light chain disease are eligible) 4. Pregnant or breast-feeding 5. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis. 6. Patients who have undergone prior allograft or autologous transplant 7. Prior solid organ transplant 8. Patients receiving prior radiation to more than 20% of bone marrow containing areas
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze | Up to 1 year post-transplant. | To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation. |
Countries
United States
Participant flow
Recruitment details
1 ineligible
Participants by arm
| Arm | Count |
|---|---|
| Total Marrow Irradiation Escalating doses of total marrow irradiation (3Gy, 6Gy, 9Gy, or 12Gy) with standard high dose melphalan prior to autologous stem cell rescue.
Total Marrow Irradiation: Subjects in this trial will receive total body irradiation (3Gy) per day for up to four days and as little as one day. Total IMT doses: 3Gy, 6Gy, 9Gy, or 12Gy.
Autologous Transplant: Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning with escalating doses of total marrow irradiation prior to autologous stem cell rescue.
Melphalan: Subjects will receive standard melphalan 200mg/m\^2 (100mg/m\^2 day-2 and day-1) conditioning therapy prior to transplant.
Filgrastim (G-CSF): Subjects to begin GCSF 5 μg/kg/d SC or IV on Day 5 and continue until ANC \> 1000/mm\^3 over period of 3 days. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Total Marrow Irradiation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Progression Free Survival No Results Due to 1 Subject Came Off Treatment Within 7 Days and 1 Subject Came Off Treatment Within 5 Days. Not Enough Data to Analyze
To evaluate progression free survival (PFS) and in patients with multiple myeloma undergoing autologous stem cell transplant using the combination of high dose melphalan and total marrow irradiation.
Time frame: Up to 1 year post-transplant.
Population: Data not collected