Trial Outcomes & Findings for Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401) (NCT NCT02728102)
NCT ID: NCT02728102
Last Updated: 2024-05-07
Results Overview
The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
203 participants
Primary outcome timeframe
1 year
Results posted on
2024-05-07
Participant Flow
The study opened to accrual on July 25, 2016 and closed to accrual on October 12, 2018 with 203 participants enrolled from 18 participating centers. The final study database lock was done September 9, 2021.
Sixty-three participants dropped out of the study prior to randomization and 140 participants received a transplant and proceeded to randomization. The reasons for dropout include insufficient tumor cells collected (n=13), withdrew consent from study (n=12), ineligible to be randomized (n=8), disease progression prior to randomization (n=6), refused or did not make it to transplantation (n=10), physician decision (n=7), manufacturing failure (n=4), lost to follow up (n=2), and insurance (n=1).
Participant milestones
| Measure |
Lenalidomide, Vaccine, and GM-CSF
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide and GM-CSF
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Overall Study
STARTED
|
68
|
37
|
35
|
|
Overall Study
COMPLETED
|
61
|
33
|
30
|
|
Overall Study
NOT COMPLETED
|
7
|
4
|
5
|
Reasons for withdrawal
| Measure |
Lenalidomide, Vaccine, and GM-CSF
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide and GM-CSF
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Overall Study
Death
|
3
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
3
|
|
Overall Study
Physician Decision
|
1
|
1
|
0
|
|
Overall Study
Investigational study drug permanently discontinued
|
3
|
1
|
0
|
|
Overall Study
Covid
|
0
|
0
|
1
|
Baseline Characteristics
Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)
Baseline characteristics by cohort
| Measure |
Total
n=140 Participants
Total of all reporting groups
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide and GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
|---|---|---|---|---|
|
Age, Continuous
|
60.0 years
n=4 Participants
|
59.1 years
n=5 Participants
|
59.3 years
n=5 Participants
|
62.3 years
n=7 Participants
|
|
Sex: Female, Male
Female
|
63 Participants
n=4 Participants
|
18 Participants
n=5 Participants
|
27 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
77 Participants
n=4 Participants
|
17 Participants
n=5 Participants
|
41 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=4 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
124 Participants
n=4 Participants
|
30 Participants
n=5 Participants
|
61 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=4 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=4 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=4 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=4 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=4 Participants
|
5 Participants
n=5 Participants
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
112 Participants
n=4 Participants
|
28 Participants
n=5 Participants
|
54 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=4 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=4 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
|
Karnofsky Performance Score (KPS)
100
|
32 Participants
n=4 Participants
|
9 Participants
n=5 Participants
|
16 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
|
Karnofsky Performance Score (KPS)
90
|
53 Participants
n=4 Participants
|
14 Participants
n=5 Participants
|
29 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
|
Karnofsky Performance Score (KPS)
80
|
41 Participants
n=4 Participants
|
9 Participants
n=5 Participants
|
17 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
|
Karnofsky Performance Score (KPS)
70
|
14 Participants
n=4 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
|
Disease Response at Randomization
Stringent Complete Response (sCR)
|
21 Participants
n=4 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
|
Disease Response at Randomization
Complete Response (CR)
|
29 Participants
n=4 Participants
|
9 Participants
n=5 Participants
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
|
Disease Response at Randomization
Very Good Partial Response (VGPR)
|
69 Participants
n=4 Participants
|
17 Participants
n=5 Participants
|
37 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
|
Disease Response at Randomization
Partial Response (PR)
|
21 Participants
n=4 Participants
|
5 Participants
n=5 Participants
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
|
Disease Response at Randomization
Stable Response
|
0 Participants
n=4 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: The primary analysis population includes all the randomized participants. Protocol defines primary analysis is to compare participants receiving vaccine vs those without vaccine. So no vaccine arms with or without GM-CSF are combined. Four participants withdrew consent to all study procedures before 1-year post-transplant. Of these, 2 cases on the Lenalidomide/GM-CSF arm and 2 cases on the Lenalidomide Alone arm. These participants were not evaluable for the primary endpoint and ERC confirmed.
The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With 1-year Response Rate of CR/sCR
|
52.9 percentage of participants
Interval 44.5 to 61.3
|
50.0 percentage of participants
Interval 41.6 to 58.4
|
—
|
SECONDARY outcome
Timeframe: 6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapyPopulation: Analysis Population includes transplanted participants.
A participant's disease status is evaluated based on the International Uniform Response Criteria per protocol. Before disease progression (PD), all disease classifications including stringent complete response (sCR), complete response (CR), very good partial remission (VGPR), partial response (PR), stable disease (SD) are relative to participant's disease status at study entry. Disease status is 'Not Evaluable' when disease assessment is not required, or disease status is missing.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Participants Response to Treatment
Disease Status at 6 Months · Stringent Complete Response (sCR)
|
12 Participants
|
9 Participants
|
8 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Complete Response (CR)
|
17 Participants
|
8 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Very Good Partial Remission (VGPR)
|
28 Participants
|
12 Participants
|
13 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Partial Response (PR)
|
5 Participants
|
5 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Stable Disease (SD)
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Progression (PD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 6 Months · Not Evaluable
|
4 Participants
|
2 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Stringent Complete Response (sCR)
|
18 Participants
|
8 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Complete Response (CR)
|
18 Participants
|
8 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Very Good Partial Remission (VGPR)
|
22 Participants
|
12 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Partial Response (PR)
|
4 Participants
|
7 Participants
|
3 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Progression (PD)
|
5 Participants
|
0 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Dead
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 12 Months · Not Evaluable
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Stringent Complete Response (sCR)
|
17 Participants
|
7 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Complete Response (CR)
|
13 Participants
|
6 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Very Good Partial Remission (VGPR)
|
15 Participants
|
15 Participants
|
3 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Partial Response (PR)
|
6 Participants
|
4 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Progression (PD)
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Dead
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at 24 Months · Not Evaluable
|
13 Participants
|
5 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Stringent Complete Response (sCR)
|
8 Participants
|
9 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Complete Response (CR)
|
19 Participants
|
5 Participants
|
14 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Very Good Partial Remission (VGPR)
|
35 Participants
|
15 Participants
|
11 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Partial Response (PR)
|
5 Participants
|
6 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Progression (PD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 3 (Day 57 Assessment) · Not Evaluable
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Stringent Complete Response (sCR)
|
13 Participants
|
7 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Complete Response (CR)
|
18 Participants
|
7 Participants
|
14 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Very Good Partial Remission (VGPR)
|
28 Participants
|
14 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Partial Response (PR)
|
6 Participants
|
7 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Stable Disease (SD)
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Progression (PD)
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 6 (Day 141 Assessment) · Not Evaluable
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Stringent Complete Response (sCR)
|
16 Participants
|
8 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Complete Response (CR)
|
17 Participants
|
7 Participants
|
15 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Very Good Partial Remission (VGPR)
|
24 Participants
|
13 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Partial Response (PR)
|
6 Participants
|
7 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Progression (PD)
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 9 (Day 225 Assessment) · Not Evaluable
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Stringent Complete Response (sCR)
|
18 Participants
|
9 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Complete Response (CR)
|
18 Participants
|
6 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Very Good Partial Remission (VGPR)
|
20 Participants
|
13 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Partial Response (PR)
|
5 Participants
|
7 Participants
|
4 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Progression (PD)
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 12 (Day 309 Assessment) · Not Evaluable
|
7 Participants
|
2 Participants
|
3 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Stringent Complete Response (sCR)
|
18 Participants
|
9 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Complete Response (CR)
|
17 Participants
|
5 Participants
|
13 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Very Good Partial Remission (VGPR)
|
18 Participants
|
11 Participants
|
6 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Partial Response (PR)
|
4 Participants
|
7 Participants
|
2 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Progression (PD)
|
3 Participants
|
0 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 15 (Day 393 Assessment) · Not Evaluable
|
8 Participants
|
5 Participants
|
4 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Stringent Complete Response (sCR)
|
20 Participants
|
7 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Complete Response (CR)
|
16 Participants
|
7 Participants
|
13 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Very Good Partial Remission (VGPR)
|
17 Participants
|
14 Participants
|
6 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Partial Response (PR)
|
3 Participants
|
6 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Stable Disease (SD)
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Progression (PD)
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Dead
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 18 (Day 477 Assessment) · Not Evaluable
|
9 Participants
|
3 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Stringent Complete Response (sCR)
|
20 Participants
|
6 Participants
|
10 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Complete Response (CR)
|
15 Participants
|
5 Participants
|
11 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Very Good Partial Remission (VGPR)
|
14 Participants
|
17 Participants
|
6 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Partial Response (PR)
|
5 Participants
|
4 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Progression (PD)
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Dead
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 21 (Day 561 Assessment) · Not Evaluable
|
11 Participants
|
5 Participants
|
7 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Stringent Complete Response (sCR)
|
19 Participants
|
6 Participants
|
9 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Complete Response (CR)
|
15 Participants
|
7 Participants
|
11 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Very Good Partial Remission (VGPR)
|
14 Participants
|
16 Participants
|
6 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Partial Response (PR)
|
6 Participants
|
3 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Stable Disease (SD)
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Progression (PD)
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Dead
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Participants Response to Treatment
Disease Status at Cycle 24 (Day 654 Assessment) · Not Evaluable
|
12 Participants
|
4 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis.
The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm and the combined non-vaccine arms using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms
|
20.7 percentage of participants
Interval 12.0 to 31.1
|
11.8 percentage of participants
Interval 5.5 to 20.7
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis.
This is the pairwise comparison for percentage of participants with Myeloma Progression. The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Myeloma Progression in Pairwise Analysis
|
20.7 percentage of participants
Interval 12.0 to 31.1
|
8.7 percentage of participants
Interval 2.2 to 21.0
|
15.1 percentage of participants
Interval 5.4 to 29.4
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
TRM is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for TRM. Patients alive without disease progression at last contact are considered censored for this event. TRM from time of randomization will be compared between vaccine and no-vaccine arms combined starting at time of randomization.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Treatment-related Mortality (TRM)
|
0 percentage of participants
Interval 0.0 to 0.0
|
0 percentage of participants
Interval 0.0 to 0.0
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine and the combined non-vaccine arms using the log-rank test.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Progression-Free Survival
|
79.3 percentage of participants
Interval 67.6 to 87.2
|
88.2 percentage of participants
Interval 77.8 to 93.3
|
—
|
SECONDARY outcome
Timeframe: 2 yearPopulation: The randomized participants are included in the analysis
This is the pairwise comparison for percentage of participants with Progression-Free Survival. Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Progression-Free Survival in Pairwise Analysis
|
79.3 percentage of participants
Interval 67.6 to 87.2
|
91.3 percentage of participants
Interval 75.5 to 97.1
|
84.9 percentage of participants
Interval 67.5 to 93.4
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine and the combined non-vaccine arms from time of randomization.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Overall Survival
|
97 percentage of participants
Interval 88.6 to 99.2
|
98.5 percentage of participants
Interval 89.7 to 99.8
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
This is the pairwise comparison for percentage of participants with Overall Survival. Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm from time of randomization.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Overall Survival in Pairwise Analysis
|
97 percentage of participants
Interval 88.6 to 99.2
|
100 percentage of participants
Interval 100.0 to 100.0
|
96.9 percentage of participants
Interval 79.8 to 99.6
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. All Grade ≥ 3 toxicities will be tabulated for treatment arms. Toxicities are categorized by organ system according to the CTCAE. Toxicities that involve multiple questions per organ system are combined in one category.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Number of Grade ≥ 3 Toxicities
Investigations
|
2 Toxicities
|
0 Toxicities
|
1 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Metabolism and Nutrition Disorders
|
7 Toxicities
|
1 Toxicities
|
3 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Musculoskeletal and Connective Tissue Disorders
|
1 Toxicities
|
1 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Nervous System Disorders
|
14 Toxicities
|
5 Toxicities
|
1 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Renal Disorders
|
1 Toxicities
|
0 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Respiratory, Thoracic and Mediastinal Disorders
|
5 Toxicities
|
1 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Skin and Subcutaneous Tissue Disorders
|
4 Toxicities
|
5 Toxicities
|
7 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Vascular Disorders
|
6 Toxicities
|
11 Toxicities
|
3 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Abnormal Liver Symptoms
|
0 Toxicities
|
1 Toxicities
|
0 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Auditory Disorders
|
1 Toxicities
|
0 Toxicities
|
0 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Blood and Lymphatic Disorders
|
81 Toxicities
|
40 Toxicities
|
38 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Cardiovascular Disorders
|
4 Toxicities
|
3 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
GI Disorders
|
15 Toxicities
|
4 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
General Disorders
|
5 Toxicities
|
2 Toxicities
|
2 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Hepatobiliary/Pancreas Disorders
|
4 Toxicities
|
1 Toxicities
|
1 Toxicities
|
|
Number of Grade ≥ 3 Toxicities
Immune System Disorders
|
2 Toxicities
|
0 Toxicities
|
0 Toxicities
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. The number of participants experiencing Grade ≥ 3 toxicity are displayed for the vaccine and non-vaccine arms separately. The proportion of participants experiencing Grade ≥ 3 toxicity are compared between the vaccine and non-vaccine arms combined.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Participants With Grade ≥ 3 Toxicities
|
53 Participants
|
49 Participants
|
—
|
SECONDARY outcome
Timeframe: 2yearsPopulation: The randomized participants are included in the analysis
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after randomization will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Number of Grade 2 and 3 Infections
Other
|
1 infections
|
0 infections
|
1 infections
|
|
Number of Grade 2 and 3 Infections
Bacterial
|
10 infections
|
3 infections
|
6 infections
|
|
Number of Grade 2 and 3 Infections
Viral
|
14 infections
|
6 infections
|
14 infections
|
|
Number of Grade 2 and 3 Infections
Fungal
|
0 infections
|
0 infections
|
0 infections
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine and the combined non-vaccine groups using the Gray's test.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=72 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Grade 2 and 3 Infections
|
26.6 percentage of participants
Interval 16.7 to 37.6
|
23.2 percentage of participants
Interval 14.0 to 33.8
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The randomized participants are included in the analysis
This is the pairwise comparison for percentage of participants with Grade 2 and 3 infections. Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using the Gray's test.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=37 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis
|
26.6 percentage of participants
Interval 16.7 to 37.6
|
14.2 percentage of participants
Interval 5.1 to 27.8
|
32.6 percentage of participants
Interval 17.5 to 48.7
|
SECONDARY outcome
Timeframe: Pre-randomization, Post-randomization at Cycle 9Population: The randomized participants who had MRD assessment. Participants who did not have MRD assessment are not included in this analysis.
Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. Multichannel flow cytometry will be used to establish MRD based on the presence of malignant plasma cells that are CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The number of patients with MRD negative (MRD-) are described using frequencies at pre-randomization and 9th cycle post-randomization and compared between the vaccine arm with the no-vaccine arms combined.
Outcome measures
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=65 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide With or Without GM-CSF
n=66 Participants
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Number of Participants With Minimal Residual Disease (MRD)
Pre-randomization
|
35 Participants
|
31 Participants
|
—
|
|
Number of Participants With Minimal Residual Disease (MRD)
Post-randomization at Cycle 9
|
38 Participants
|
41 Participants
|
—
|
Adverse Events
Lenalidomide, Vaccine, and GM-CSF
Serious events: 2 serious events
Other events: 3 other events
Deaths: 3 deaths
Lenalidomide and GM-CSF
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Maintenance Lenalidomide
Serious events: 1 serious events
Other events: 3 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide and GM-CSF
n=37 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
NEUTROPENIC FEVER
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
PROLONGED QTC
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
ELEVATE LIVER ENZYMES
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Nervous system disorders
SYNCOPE
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Cardiac disorders
ATRIAL FLUTTER
|
0.00%
0/68 • 2 years
|
0.00%
0/37 • 2 years
|
2.9%
1/35 • Number of events 1 • 2 years
|
|
Cardiac disorders
CONGESTIVE HEART FAILURE
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOMA
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
LIVER FUNCTION TESTS INCREASED
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
Other adverse events
| Measure |
Lenalidomide, Vaccine, and GM-CSF
n=68 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation.
Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Myeloma vaccine: The target dose is 3 x 10\^6 fusion cells per vaccine. A minimum of 3 x 10\^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance.
GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.
|
Lenalidomide and GM-CSF
n=37 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
|
Maintenance Lenalidomide
n=35 participants at risk
Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.
Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).
Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10\^6 CD34+ cells/kg patient actual body weight per autologous transplantation.
Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m\^2 at the schedule and timing according to institutional practices.
Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
|
|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LENTIGO MALIGNA
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
ELEVATED ALT
|
1.5%
1/68 • Number of events 1 • 2 years
|
0.00%
0/37 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
INCREASED ALT > 3.0 X ULN
|
0.00%
0/68 • 2 years
|
0.00%
0/37 • 2 years
|
2.9%
1/35 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
|
0.00%
0/68 • 2 years
|
0.00%
0/37 • 2 years
|
2.9%
1/35 • Number of events 1 • 2 years
|
|
Investigations
ELEVATED LFT
|
0.00%
0/68 • 2 years
|
0.00%
0/37 • 2 years
|
2.9%
1/35 • Number of events 1 • 2 years
|
|
Vascular disorders
GRADE 2 DVT
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
|
Investigations
GRADE 2 TRANSAMINITIS
|
0.00%
0/68 • 2 years
|
2.7%
1/37 • Number of events 1 • 2 years
|
0.00%
0/35 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place