NCT02728102 · OUTCOME

Percentage of Participants With 1-year Response Rate of CR/sCR

Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401) · Source last updated 2024-05-07

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure: NUMBER
Unit: percentage of participants
Interval / dispersion: 80% Confidence Interval
Time frame: 1 year

What was measured

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.

Analysis population: 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.

Groups in this outcome

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 With or Without GM-CSF

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.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

Group	Source count
Lenalidomide, Vaccine, and GM-CSF	68
Lenalidomide With or Without GM-CSF	68

Reported measurements

Source class 1

Values in percentage of participants · Interval/dispersion: 80% Confidence Interval
Group	Value	Spread	Lower	Upper	Comment
Lenalidomide, Vaccine, and GM-CSF	52.9	Not reported	44.5	61.3	Not reported
Lenalidomide With or Without GM-CSF	50.0	Not reported	41.6	58.4	Not reported

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

ci Lower Limit
-8.8
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
14.6
group Description
The proportion of patients alive and in CR/sCR at 1 year post transplant will be described in the vaccine and no vaccine groups with 80% confidence intervals and compared between groups using a two-sample Z test comparing binomial proportions.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
p Value
0.3657
p Value Comment
A one-sided significance level of 0.10 is used to assess whether the vaccine appears promising relative to control.
param Type
difference in the proportions
param Value
2.9
statistical Method
Z test
ci Lower Limit
0.70
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
2.03
estimate Comment
The Cochran-Mantel-Haenszel Odds Ratio estimate is for the Stratification. Stratum 1 is sCR/CR at Randomization. Stratum 2 is VGPR/PR/Stable Response at Randomization.
group Description
A secondary analysis stratified on disease response prior to randomization between arms will be conducted using a Cochran-Mantel-Haenszel test, and a stratified odds ratio along with 80% confidence intervals will be estimated.
group Ids
OG000
OG001
non Inferiority Comment
The stratified odds ratio is estimated with 80% confidence intervals.
non Inferiority Type
EQUIVALENCE
p Value
0.7461
p Value Comment
P-value is provided by Breslow-Day Test for Homogeneity of the Odds Ratios.
param Type
Odds Ratio (OR)
param Value
1.19
statistical Method
Cochran-Mantel-Haenszel
ci Lower Limit
-6.4
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
20.6
group Description
A secondary pairwise analysis of CR/sCR rates comparing the vaccine arm to Lenalidomide/GM-CSF arm at 1 year post transplant.
group Ids
OG000
OG001
non Inferiority Comment
The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide/GM-CSF arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
non Inferiority Type
SUPERIORITY
p Value
0.2429
param Type
difference in the proportions
param Value
7.2
statistical Method
Z test
ci Lower Limit
-15.6
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
12.4
group Description
A secondary pairwise analysis of CR rates comparing the vaccine arm to Lenalidomide alone arm at 1 year post transplant.
group Ids
OG000
OG001
non Inferiority Comment
The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide alone arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
non Inferiority Type
SUPERIORITY
p Value
0.4397
param Type
difference in the proportions
param Value
-1.6
statistical Method
Z test

Complete source fields

analyses

ci Lower Limit
-8.8
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
14.6
group Description
The proportion of patients alive and in CR/sCR at 1 year post transplant will be described in the vaccine and no vaccine groups with 80% confidence intervals and compared between groups using a two-sample Z test comparing binomial proportions.
group Ids
OG000
OG001
non Inferiority Type
SUPERIORITY
p Value
0.3657
p Value Comment
A one-sided significance level of 0.10 is used to assess whether the vaccine appears promising relative to control.
param Type
difference in the proportions
param Value
2.9
statistical Method
Z test
ci Lower Limit
0.70
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
2.03
estimate Comment
The Cochran-Mantel-Haenszel Odds Ratio estimate is for the Stratification. Stratum 1 is sCR/CR at Randomization. Stratum 2 is VGPR/PR/Stable Response at Randomization.
group Description
A secondary analysis stratified on disease response prior to randomization between arms will be conducted using a Cochran-Mantel-Haenszel test, and a stratified odds ratio along with 80% confidence intervals will be estimated.
group Ids
OG000
OG001
non Inferiority Comment
The stratified odds ratio is estimated with 80% confidence intervals.
non Inferiority Type
EQUIVALENCE
p Value
0.7461
p Value Comment
P-value is provided by Breslow-Day Test for Homogeneity of the Odds Ratios.
param Type
Odds Ratio (OR)
param Value
1.19
statistical Method
Cochran-Mantel-Haenszel
ci Lower Limit
-6.4
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
20.6
group Description
A secondary pairwise analysis of CR/sCR rates comparing the vaccine arm to Lenalidomide/GM-CSF arm at 1 year post transplant.
group Ids
OG000
OG001
non Inferiority Comment
The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide/GM-CSF arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
non Inferiority Type
SUPERIORITY
p Value
0.2429
param Type
difference in the proportions
param Value
7.2
statistical Method
Z test
ci Lower Limit
-15.6
ci Num Sides
TWO_SIDED
ci Pct Value
80
ci Upper Limit
12.4
group Description
A secondary pairwise analysis of CR rates comparing the vaccine arm to Lenalidomide alone arm at 1 year post transplant.
group Ids
OG000
OG001
non Inferiority Comment
The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide alone arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
non Inferiority Type
SUPERIORITY
p Value
0.4397
param Type
difference in the proportions
param Value
-1.6
statistical Method
Z test

classes

categories
measurements
group Id
OG000
lower Limit
44.5
upper Limit
61.3
value
52.9
group Id
OG001
lower Limit
41.6
upper Limit
58.4
value
50.0

denoms

counts
group Id
OG000
value
68
group Id
OG001
value
68
units
Participants

description

dispersion Type

80% Confidence Interval

groups

description
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.
id
OG000
title
Lenalidomide, Vaccine, and GM-CSF
description
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.
id
OG001
title
Lenalidomide With or Without GM-CSF

param Type

NUMBER

population Description

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.

reporting Status

POSTED

time Frame

1 year

title

Percentage of Participants With 1-year Response Rate of CR/sCR

type

PRIMARY

unit Of Measure

percentage of participants

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Preserved source evidence · Not medical advice