Multiple Myeloma
Conditions
Keywords
multiple myeloma
Brief summary
Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant. Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant. Study Objectives: Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year. Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.
Interventions
BIOLOGICALActivated marrow infiltrating lymphocytes
Administered on Days 3 and 4.
BIOLOGICALAllogeneic Myeloma Vaccine
Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.
DRUGCyclophosphamide
Administered at 2.5 g/m\^2.
BIOLOGICALFilgrastim
Administered post cyclophosphamide daily until leukapheresis.
PROCEDURELeukapheresis
Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
DRUGMelphalan
100 mg/m\^2/day given on Days -2 and -1.
BIOLOGICALAutologous stem cell transplant
Infused on Day 0.
Sponsors
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Durie-Salmon Stage II or III multiple myeloma * Newly diagnosed either prior to receiving treatment or having completed induction therapy * Relapsed myeloma not previously transplanted within the past 5 years * Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable * Age greater than 18 years old * ECOG performance status of 0 - 2 * Meet all institutional requirements for autologous stem cell transplantation * The patient must be able to comprehend and have signed the informed consent
Exclusion criteria
* Diagnosis of any of the following plasma cell disorders: 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 * Amyloidosis * Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection * Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine * In a complete remission at the time of bone marrow collection * Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection * Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device * History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer * Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted * Evidence of spinal cord compression at time of transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates by Blade Criteria | Up to 1 year | Number of participants with each disease response category utilizing the Blade criteria: * Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. * Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with \< 5% plasma cells. * Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein \< 100 mg/24 hours. * Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein. * Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein. * Stable Disease (SD): Defined as not falling into any other response category. * Overall response rate (ORR): Total of CR, nCR, VGPR, and PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Up to 5 years | Median number of months that participants were alive without disease relapse or progression (progression-free survival). |
| Overall Survival | Up to 5 years | Number of participants alive at 5 years (overall survival). |
| Feasibility as Measured by Participant Withdrawal or Removal | Up to 1 year | Number of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion. |
| Safety as Measured by Grade 3-5 Adverse Events | Up to 1 year | Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to MILs or the myeloma vaccine. |
| Anti-tumor Immune Response | Days 60, 180, and 360 | * Evaluate tumor specific responses in blood and bone marrow * Examine T cell responses to DC-pulsed myeloma cell lines * Examine induction of novel antibody responses |
| The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio) | Days 60, 180, and 360 | — |
| The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels) | Days 60, 180, 360 | Serum C Telopeptide |
| The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels) | Days 60, 180, 360 | bAlkaline phosphatase |
| The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels) | Days 60, 180, 360 | Osteocalcin |
| Effect of aMILs on Clonogenic Myeloma Precursors | Days 60, 180, and 360 | • Examine side population of CD19 enriched PBLs throughout study. |
Countries
United States
Participant flow
Pre-assignment details
One subject was a screen failure.
Participants by arm
| Arm | Count |
|---|---|
| ASCT + MILs Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. | 17 |
| ASCT + MILs + Vaccine Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300. | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 3 | 2 |
Baseline characteristics
| Characteristic | ASCT + MILs | Total | ASCT + MILs + Vaccine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 13 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 22 Participants | 11 Participants |
| Age, Continuous | 59 years | 60 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 34 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| International Staging System (ISS) stage Stage 1 | 7 Participants | 15 Participants | 8 Participants |
| International Staging System (ISS) stage Stage 2 | 3 Participants | 7 Participants | 4 Participants |
| International Staging System (ISS) stage Stage 3 | 3 Participants | 8 Participants | 5 Participants |
| International Staging System (ISS) stage Stage unknown | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 28 Participants | 15 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 25 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 17 | 6 / 18 |
| other Total, other adverse events | 6 / 17 | 15 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 18 |
Outcome results
Primary
Response Rates by Blade Criteria
Number of participants with each disease response category utilizing the Blade criteria: * Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with \< 5% plasma cells. * Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with \< 5% plasma cells. * Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein \< 100 mg/24 hours. * Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein. * Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein. * Stable Disease (SD): Defined as not falling into any other response category. * Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.
Time frame: Up to 1 year
Population: Only participants who had ASCT were evaluated for response. Three participants on the ASCT + MILs arm and two participants on the ASCT + MILs + vaccine arm were removed from study prior to ASCT and were therefore not evaluable for this outcome.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ASCT + MILs | Response Rates by Blade Criteria | VGPR | 1 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | MR | 0 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | nCR | 3 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | SD | 4 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | PR | 4 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | ORR | 10 Participants |
| ASCT + MILs | Response Rates by Blade Criteria | CR | 2 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | ORR | 13 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | CR | 5 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | nCR | 2 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | VGPR | 1 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | PR | 5 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | MR | 1 Participants |
| ASCT + MILs + Vaccine | Response Rates by Blade Criteria | SD | 2 Participants |
Secondary
Anti-tumor Immune Response
* Evaluate tumor specific responses in blood and bone marrow * Examine T cell responses to DC-pulsed myeloma cell lines * Examine induction of novel antibody responses
Time frame: Days 60, 180, and 360
Population: This measure was not assessed. Data was not collected.
Secondary
Effect of aMILs on Clonogenic Myeloma Precursors
• Examine side population of CD19 enriched PBLs throughout study.
Time frame: Days 60, 180, and 360
Population: This measure was not assessed. Data was not collected.
Secondary
Feasibility as Measured by Participant Withdrawal or Removal
Number of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASCT + MILs | Feasibility as Measured by Participant Withdrawal or Removal | 3 Participants |
| ASCT + MILs + Vaccine | Feasibility as Measured by Participant Withdrawal or Removal | 3 Participants |
Secondary
Overall Survival
Number of participants alive at 5 years (overall survival).
Time frame: Up to 5 years
Population: Only participants who had ASCT were evaluated for response. Three participants on the ASCT + MILs arm and two participants on the ASCT + MILs + vaccine arm were removed from study prior to ASCT and were therefore not evaluable for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASCT + MILs | Overall Survival | 7 Participants |
| ASCT + MILs + Vaccine | Overall Survival | 9 Participants |
Secondary
Progression-free Survival
Median number of months that participants were alive without disease relapse or progression (progression-free survival).
Time frame: Up to 5 years
Population: Only participants who had ASCT were evaluated for response. Three participants on the ASCT + MILs arm and two participants on the ASCT + MILs + vaccine arm were removed from study prior to ASCT and were therefore not evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ASCT + MILs | Progression-free Survival | 15.5 months |
| ASCT + MILs + Vaccine | Progression-free Survival | 18.6 months |
Secondary
Safety as Measured by Grade 3-5 Adverse Events
Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to MILs or the myeloma vaccine.
Time frame: Up to 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ASCT + MILs | Safety as Measured by Grade 3-5 Adverse Events | 0 Participants |
| ASCT + MILs + Vaccine | Safety as Measured by Grade 3-5 Adverse Events | 1 Participants |
Secondary
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)
bAlkaline phosphatase
Time frame: Days 60, 180, 360
Population: This measure was not assessed. Data was not collected.
Secondary
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)
Osteocalcin
Time frame: Days 60, 180, 360
Population: This measure was not assessed. Data was not collected.
Secondary
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)
Time frame: Days 60, 180, and 360
Population: This measure was not assessed. Data was not collected.
Secondary
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)
Serum C Telopeptide
Time frame: Days 60, 180, 360
Population: This measure was not assessed. Data was not collected.