Trial Outcomes & Findings for Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma (NCT NCT01045460)
NCT ID: NCT01045460
Last Updated: 2021-04-09
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Up to 1 year
Results posted on
2021-04-09
Participant Flow
One subject was a screen failure.
Participant milestones
| Measure |
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.
Activated marrow infiltrating lymphocytes: Administered on Days 3 and 4.
Cyclophosphamide: Administered at 2.5 g/m\^2.
Filgrastim: Administered post cyclophosphamide daily until leukapheresis.
Leukapheresis: Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Melphalan: 100 mg/m\^2/day given on Days -2 and -1.
Autologous stem cell transplant: Infused on Day 0.
|
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.
Activated marrow infiltrating lymphocytes: Administered on Days 3 and 4.
Allogeneic Myeloma Vaccine: Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.
Cyclophosphamide: Administered at 2.5 g/m\^2.
Filgrastim: Administered post cyclophosphamide daily until leukapheresis.
Leukapheresis: Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Melphalan: 100 mg/m\^2/day given on Days -2
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
18
|
|
Overall Study
COMPLETED
|
11
|
15
|
|
Overall Study
NOT COMPLETED
|
6
|
3
|
Reasons for withdrawal
| Measure |
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.
Activated marrow infiltrating lymphocytes: Administered on Days 3 and 4.
Cyclophosphamide: Administered at 2.5 g/m\^2.
Filgrastim: Administered post cyclophosphamide daily until leukapheresis.
Leukapheresis: Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Melphalan: 100 mg/m\^2/day given on Days -2 and -1.
Autologous stem cell transplant: Infused on Day 0.
|
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.
Activated marrow infiltrating lymphocytes: Administered on Days 3 and 4.
Allogeneic Myeloma Vaccine: Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.
Cyclophosphamide: Administered at 2.5 g/m\^2.
Filgrastim: Administered post cyclophosphamide daily until leukapheresis.
Leukapheresis: Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
Melphalan: 100 mg/m\^2/day given on Days -2
|
|---|---|---|
|
Overall Study
Physician Decision
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
3
|
0
|
Baseline Characteristics
Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma
Baseline characteristics by cohort
| Measure |
ASCT + MILs
n=17 Participants
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.
|
ASCT + MILs + Vaccine
n=18 Participants
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.
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
International Staging System (ISS) stage
Stage 1
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
International Staging System (ISS) stage
Stage 2
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
International Staging System (ISS) stage
Stage 3
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
International Staging System (ISS) stage
Stage unknown
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Continuous
|
59 years
n=5 Participants
|
63 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
16 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 1 yearPopulation: 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.
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.
Outcome measures
| Measure |
ASCT + MILs
n=14 Participants
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.
|
ASCT + MILs + Vaccine
n=16 Participants
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.
|
|---|---|---|
|
Response Rates by Blade Criteria
CR
|
2 Participants
|
5 Participants
|
|
Response Rates by Blade Criteria
nCR
|
3 Participants
|
2 Participants
|
|
Response Rates by Blade Criteria
VGPR
|
1 Participants
|
1 Participants
|
|
Response Rates by Blade Criteria
PR
|
4 Participants
|
5 Participants
|
|
Response Rates by Blade Criteria
MR
|
0 Participants
|
1 Participants
|
|
Response Rates by Blade Criteria
SD
|
4 Participants
|
2 Participants
|
|
Response Rates by Blade Criteria
ORR
|
10 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: 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.
Median number of months that participants were alive without disease relapse or progression (progression-free survival).
Outcome measures
| Measure |
ASCT + MILs
n=14 Participants
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.
|
ASCT + MILs + Vaccine
n=16 Participants
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.
|
|---|---|---|
|
Progression-free Survival
|
15.5 months
Interval 13.0 to 37.0
|
18.6 months
Interval 13.0 to 27.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: 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.
Number of participants alive at 5 years (overall survival).
Outcome measures
| Measure |
ASCT + MILs
n=14 Participants
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.
|
ASCT + MILs + Vaccine
n=16 Participants
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.
|
|---|---|---|
|
Overall Survival
|
7 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearNumber of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion.
Outcome measures
| Measure |
ASCT + MILs
n=17 Participants
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.
|
ASCT + MILs + Vaccine
n=18 Participants
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.
|
|---|---|---|
|
Feasibility as Measured by Participant Withdrawal or Removal
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearNumber 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.
Outcome measures
| Measure |
ASCT + MILs
n=17 Participants
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.
|
ASCT + MILs + Vaccine
n=18 Participants
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.
|
|---|---|---|
|
Safety as Measured by Grade 3-5 Adverse Events
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Days 60, 180, and 360Population: This measure was not assessed. Data was not collected.
* 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
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 60, 180, and 360Population: This measure was not assessed. Data was not collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 60, 180, 360Population: This measure was not assessed. Data was not collected.
Serum C Telopeptide
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 60, 180, 360Population: This measure was not assessed. Data was not collected.
bAlkaline phosphatase
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 60, 180, 360Population: This measure was not assessed. Data was not collected.
Osteocalcin
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Days 60, 180, and 360Population: This measure was not assessed. Data was not collected.
• Examine side population of CD19 enriched PBLs throughout study.
Outcome measures
Outcome data not reported
Adverse Events
ASCT + MILs
Serious events: 0 serious events
Other events: 6 other events
Deaths: 7 deaths
ASCT + MILs + Vaccine
Serious events: 0 serious events
Other events: 15 other events
Deaths: 6 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ASCT + MILs
n=17 participants at risk
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.
|
ASCT + MILs + Vaccine
n=18 participants at risk
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.
|
|---|---|---|
|
Investigations
Anemia
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Gastrointestinal disorders
Diarrhea
|
17.6%
3/17 • Number of events 3 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
27.8%
5/18 • Number of events 6 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Immune system disorders
Fever
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Immune system disorders
Flu-like symptoms
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Immune system disorders
Injection site reaction
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
77.8%
14/18 • Number of events 40 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Investigations
Pancytopenia
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Skin and subcutaneous tissue disorders
Rash
|
29.4%
5/17 • Number of events 6 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
16.7%
3/18 • Number of events 3 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
|
Investigations
Thrombocytopenia
|
0.00%
0/17 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
5.6%
1/18 • Number of events 1 • Up to 1 year
All adverse events related to MILs or vaccine administration were collected. Adverse events related to ASCT were not collected.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place