Multiple Myeloma
Conditions
Brief summary
This research is being done to find out if altering the immune system by giving activated marrow infiltrating lymphocytes (MILs) can improve outcomes for multiple myeloma patients who receive a standard autologous stem cell transplant.
Interventions
BIOLOGICALaMIL
On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide.
DRUGNo aMIL
On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide.
Sponsors
The Leukemia and Lymphoma Society
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 - 80 years old; * Patients with active myeloma requiring systemic treatment; * Newly diagnosed patients. Relapsed myeloma patients that have not previously had a transplant; * Meeting criteria for high-risk disease; * Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable; * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 (see Appendix C). * Meet all institutional requirements for autologous stem cell transplantation; * The patient must be able to comprehend and have signed the informed consent; * Patients must have had \> than PR after last therapy.
Exclusion criteria
* Diagnosis of any of the following cancers: * POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\] and skin changes); * Non-secretory myeloma (no measurable protein on Serum Free Lite Assay); * Plasma cell leukemia; * Diagnosis of amyloidosis; * Failed to achieve at least a partial response (PR) to latest therapy; * Previous hematopoietic stem cell transplantation;Patients can have had prior relapsed disease as long as they have never been previously transplanted; * Known history of HIV infection; * Use of corticosteroids (glucocorticoids) within 21 days of bone marrow collection; * Use of any myeloma-specific therapy within 21 days of bone marrow collection; * Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of registration; * Participation in any clinical trial within 28 days of registration on this trial, which involved an investigational drug or device; * History of malignancy other than multiple myeloma within five years of registration, except adequately treated basal or squamous cell skin cancer; * Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring active systemic treatment. Hypothyroidism without evidence of Grave's disease or Hashimoto's thyroiditis is permitted. * Human T-lymphotropic virus (HTLV) 1 or 2 positive; * Known hypersensitivity to Prevnar or any of its components; * Contraindication to phosphodiesterase-5 inhibitors (e.g. currently on nitrates).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | 120 days | Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | 60 days from aMILs harvest until day 60 after transplant | Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant. |
| Overall Survival (OS) | 3 years | OS assessed by number of participants alive at the end of follow up period. |
| Progression-free Survival (PFS) | 5 years | Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at four sites: Johns Hopkins University, Moffitt Cancer Center, Mayo Clinic (Jacksonville) and the Blood and Marrow Transplant Group of Georgia (Northside).
Pre-assignment details
Of the 102 patients randomized, one was randomized to the control group who was lost to follow-up prior to start; did not have aMILs harvested, and was not transplanted. This patient is therefore not included in this report.
Participants by arm
| Arm | Count |
|---|---|
| aMIL Arm Patients receive activated Marrow Infiltrating Lymphocytes (aMIL)
aMIL: On day 0, patients will receive auto transplant followed by Tadalafil and aMIL. At day 60, patients will receive Lenalidomide. | 70 |
| No aMIL Patients do not receive activated Marrow Infiltrating Lymphocytes (aMIL)
No aMIL: On day 0, patients will receive auto transplant followed by Tadalafil. At day 60, patients will receive Lenalidomide. | 31 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Disease progression | 3 | 1 |
| Overall Study | Failed expansion of cell product | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Product contamination | 2 | 0 |
Baseline characteristics
| Characteristic | aMIL Arm | No aMIL | Total |
|---|---|---|---|
| 70-gene expression Prognostic Risk Score (GEP-70) High Risk | 12 Participants | 4 Participants | 16 Participants |
| 70-gene expression Prognostic Risk Score (GEP-70) Not High Risk | 58 Participants | 27 Participants | 85 Participants |
| Age, Continuous | 62.5 years | 59.0 years | 61.7 years |
| Disease Status Newly Diagnosed | 60 Participants | 26 Participants | 86 Participants |
| Disease Status Relapsed | 10 Participants | 5 Participants | 15 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 27 Participants | 7 Participants | 34 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 or 2 | 34 Participants | 21 Participants | 55 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Missing | 9 Participants | 3 Participants | 12 Participants |
| International Staging System (ISS) Multiple Myeloma Classification missing | 14 Participants | 6 Participants | 20 Participants |
| International Staging System (ISS) Multiple Myeloma Classification Stage I | 20 Participants | 10 Participants | 30 Participants |
| International Staging System (ISS) Multiple Myeloma Classification Stage II | 19 Participants | 7 Participants | 26 Participants |
| International Staging System (ISS) Multiple Myeloma Classification Stage III | 17 Participants | 8 Participants | 25 Participants |
| Myeloma Prognostic Risk Signature (MYPRS) Risk Category High Risk | 12 Participants | 4 Participants | 16 Participants |
| Myeloma Prognostic Risk Signature (MYPRS) Risk Category Indeterminate | 25 Participants | 10 Participants | 35 Participants |
| Myeloma Prognostic Risk Signature (MYPRS) Risk Category Low Risk | 25 Participants | 15 Participants | 40 Participants |
| Myeloma Prognostic Risk Signature (MYPRS) Risk Category N/A | 8 Participants | 2 Participants | 10 Participants |
| Number of Prior Multiple Myeloma Treatments | 1 prior treatments | 2 prior treatments | 1 prior treatments |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 14 Participants | 8 Participants | 22 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 53 Participants | 21 Participants | 74 Participants |
| Region of Enrollment United States | 70 participants | 31 participants | 101 participants |
| Salmon Stage multiple myeloma classification IA-IB | 9 Participants | 0 Participants | 9 Participants |
| Salmon Stage multiple myeloma classification IIA-IIB | 14 Participants | 7 Participants | 21 Participants |
| Salmon Stage multiple myeloma classification IIIA-IIIB | 35 Participants | 21 Participants | 56 Participants |
| Salmon Stage multiple myeloma classification missing | 12 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Female | 36 Participants | 15 Participants | 51 Participants |
| Sex: Female, Male Male | 34 Participants | 16 Participants | 50 Participants |
| Time to Diagnosis | 0.53 years | 0.76 years | 0.55 years |
| Time to stem cell transplant (SCT) | 63.0 Days | 56.0 Days | 60.0 Days |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 70 | 1 / 31 |
| other Total, other adverse events | 11 / 70 | 0 / 31 |
| serious Total, serious adverse events | 64 / 70 | 29 / 31 |
Outcome results
Primary
Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product
Feasibility is defined as the ability to harvest, expand, and infuse the MILs product within 120 days. After treating 60 patients with MILs, we will declare MILs not feasible if we can only harvest, expand, and deliver MILs to 40 or fewer patients.
Time frame: 120 days
Population: 71 patients were evaluable in the feasibility set: 70 randomized to the aMILs Arm, plus one patient who was not randomized due to harvest failure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Total number who received aMILS | 71 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Feasible | 46 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- failed harvest | 1 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- disease progression | 4 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- death | 1 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- lost to follow-up | 1 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- failed expansion | 2 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- cell product contamination | 2 Participants |
| aMIL Arm | Feasibility of MILs as Assessed by the Ability to Harvest, Expand, and Infuse the MILs Product | Reason not feasible- greater than 120 days | 14 Participants |
Secondary
Overall Survival (OS)
OS assessed by number of participants alive at the end of follow up period.
Time frame: 3 years
Population: This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| aMIL Arm | Overall Survival (OS) | 55 Participants |
Secondary
Progression-free Survival (PFS)
Median PFS time equals the time of randomization (in months) until disease progression, death from any cause, or protocol deviation due to lenalidomide dosing (above 10mg), whichever occurs first.
Time frame: 5 years
Population: This is an analysis by intention-to-treat and only considers transplanted patients randomized to the aMILs arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| aMIL Arm | Progression-free Survival (PFS) | 21.82 months |
Secondary
Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events
Total number of adverse events grade 3 or higher that occur from MILs harvest through 60 days after transplant.
Time frame: 60 days from aMILs harvest until day 60 after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| aMIL Arm | Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | 129 adverse events |
| No aMIL | Toxicity as Determined by Total Number of Grade 3 or Higher Adverse Events | 65 adverse events |