Trial Outcomes & Findings for GVAX vs. Placebo for MDS/AML After Allo HSCT (NCT NCT01773395)
NCT ID: NCT01773395
Last Updated: 2022-07-18
Results Overview
Progression-Free Survival (PFS) at 18 months after randomization. Progression-free survival is defined as time from randomization to progression of disease or death whichever occurs first. Patients with relapse/progressive disease who re-enter remission after vaccination or upon withdrawal of immune suppression alone will not be considered as having disease progression. The primary analysis will be performed using the modified intention-to-treat (ITT) principle, i.e., all transplanted and eligible patients who receive at least one vaccination will be included in the analysis according to the treatment arm they are randomized to. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Progression is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
123 participants
Primary outcome timeframe
18 months
Results posted on
2022-07-18
Participant Flow
Participant milestones
| Measure |
GVAX
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Overall Study
STARTED
|
64
|
59
|
|
Overall Study
COMPLETED
|
30
|
27
|
|
Overall Study
NOT COMPLETED
|
34
|
32
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
ECOG Score at baseline was not available for one participant
Baseline characteristics by cohort
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo
Participants in the Placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64 years
n=30 Participants
|
63 years
n=27 Participants
|
63 years
n=57 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=30 Participants
|
12 Participants
n=27 Participants
|
23 Participants
n=57 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=30 Participants
|
15 Participants
n=27 Participants
|
34 Participants
n=57 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=30 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=30 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=30 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=30 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=30 Participants
|
24 Participants
n=27 Participants
|
53 Participants
n=57 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=30 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=30 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=57 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=30 Participants
|
27 participants
n=27 Participants
|
57 participants
n=57 Participants
|
|
Donor Age
|
28 years
n=30 Participants
|
30 years
n=27 Participants
|
28 years
n=57 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG 0-Fully active; no performance restrictions.
|
4 Participants
n=29 Participants • ECOG Score at baseline was not available for one participant
|
7 Participants
n=27 Participants • ECOG Score at baseline was not available for one participant
|
11 Participants
n=56 Participants • ECOG Score at baseline was not available for one participant
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG 1-Strenuous physical activity restricted; fully ambulatory and able to carry out light work.
|
18 Participants
n=29 Participants • ECOG Score at baseline was not available for one participant
|
15 Participants
n=27 Participants • ECOG Score at baseline was not available for one participant
|
33 Participants
n=56 Participants • ECOG Score at baseline was not available for one participant
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG 2-Capable of all self-care but unable to carry out any work activity Up and about >50% of time
|
7 Participants
n=29 Participants • ECOG Score at baseline was not available for one participant
|
5 Participants
n=27 Participants • ECOG Score at baseline was not available for one participant
|
12 Participants
n=56 Participants • ECOG Score at baseline was not available for one participant
|
|
Donor Sex
Female Donor
|
6 participants
n=30 Participants
|
11 participants
n=27 Participants
|
17 participants
n=57 Participants
|
|
Donor Sex
Male Donor
|
24 participants
n=30 Participants
|
16 participants
n=27 Participants
|
40 participants
n=57 Participants
|
|
Male Recipient With female Donor
|
2 participants
n=30 Participants
|
4 participants
n=27 Participants
|
6 participants
n=57 Participants
|
|
Disease Transplanted
Acute Myeloid Leukemia
|
11 Participants
n=30 Participants
|
10 Participants
n=27 Participants
|
21 Participants
n=57 Participants
|
|
Disease Transplanted
Myelodysplastic Syndrome
|
19 Participants
n=30 Participants
|
17 Participants
n=27 Participants
|
36 Participants
n=57 Participants
|
|
Acute Myeloid Leukemia Disease Status At Transplantation
2nd Complete Remission-Leukemia returned after a remission and there are now no signs of disease
|
0 Participants
n=11 Participants • Only patients with AML analyzed.
|
1 Participants
n=10 Participants • Only patients with AML analyzed.
|
1 Participants
n=21 Participants • Only patients with AML analyzed.
|
|
Acute Myeloid Leukemia Disease Status At Transplantation
Induction Failure-Leukemia has not gone away and not responded to 2 cycles of chemotherapy
|
8 Participants
n=11 Participants • Only patients with AML analyzed.
|
6 Participants
n=10 Participants • Only patients with AML analyzed.
|
14 Participants
n=21 Participants • Only patients with AML analyzed.
|
|
Acute Myeloid Leukemia Disease Status At Transplantation
Relapsed- Leukemia has returned after a period of remission
|
2 Participants
n=11 Participants • Only patients with AML analyzed.
|
3 Participants
n=10 Participants • Only patients with AML analyzed.
|
5 Participants
n=21 Participants • Only patients with AML analyzed.
|
|
Acute Myeloid Leukemia Disease Status At Transplantation
Untreated- Leukemia has never been treated
|
1 Participants
n=11 Participants • Only patients with AML analyzed.
|
0 Participants
n=10 Participants • Only patients with AML analyzed.
|
1 Participants
n=21 Participants • Only patients with AML analyzed.
|
|
AML European Leukemia Net (ELN) Risk Stratification
Favorable (Best Risk)
|
0 Participants
n=11 Participants • Only patients with AML analyzed
|
0 Participants
n=10 Participants • Only patients with AML analyzed
|
0 Participants
n=21 Participants • Only patients with AML analyzed
|
|
AML European Leukemia Net (ELN) Risk Stratification
Intermediate (Middle Risk)
|
5 Participants
n=11 Participants • Only patients with AML analyzed
|
4 Participants
n=10 Participants • Only patients with AML analyzed
|
9 Participants
n=21 Participants • Only patients with AML analyzed
|
|
AML European Leukemia Net (ELN) Risk Stratification
Adverse (Worst Risk)
|
6 Participants
n=11 Participants • Only patients with AML analyzed
|
6 Participants
n=10 Participants • Only patients with AML analyzed
|
12 Participants
n=21 Participants • Only patients with AML analyzed
|
|
Myelodysplastic Syndrome Type at Transplant
Treatment Related MDS- MDS arising from cytotoxic therapy given for a prior condition
|
3 Participants
n=19 Participants • Only patients with MDS analyzed
|
4 Participants
n=17 Participants • Only patients with MDS analyzed
|
7 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
Myelodysplastic Syndrome Type at Transplant
Non-Treatment Related MDS- Disease which has arisen with no apparent cause
|
16 Participants
n=19 Participants • Only patients with MDS analyzed
|
13 Participants
n=17 Participants • Only patients with MDS analyzed
|
29 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS Revised International Prognostic Scoring System Risk at Transplant
Good
|
10 Participants
n=19 Participants • Only patients with MDS analyzed
|
8 Participants
n=17 Participants • Only patients with MDS analyzed
|
18 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS Revised International Prognostic Scoring System Risk at Transplant
Intermediate
|
3 Participants
n=19 Participants • Only patients with MDS analyzed
|
3 Participants
n=17 Participants • Only patients with MDS analyzed
|
6 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS Revised International Prognostic Scoring System Risk at Transplant
Poor
|
4 Participants
n=19 Participants • Only patients with MDS analyzed
|
2 Participants
n=17 Participants • Only patients with MDS analyzed
|
6 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS Revised International Prognostic Scoring System Risk at Transplant
Very Poor
|
2 Participants
n=19 Participants • Only patients with MDS analyzed
|
4 Participants
n=17 Participants • Only patients with MDS analyzed
|
6 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS TP53 Mutated
No
|
14 Participants
n=19 Participants • Only patients with MDS analyzed
|
10 Participants
n=17 Participants • Only patients with MDS analyzed
|
24 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS TP53 Mutated
Yes
|
2 Participants
n=19 Participants • Only patients with MDS analyzed
|
5 Participants
n=17 Participants • Only patients with MDS analyzed
|
7 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
MDS TP53 Mutated
Not Done
|
3 Participants
n=19 Participants • Only patients with MDS analyzed
|
2 Participants
n=17 Participants • Only patients with MDS analyzed
|
5 Participants
n=36 Participants • Only patients with MDS analyzed
|
|
Cytoreductive therapy before HSCT
No
|
5 Participants
n=30 Participants
|
5 Participants
n=27 Participants
|
10 Participants
n=57 Participants
|
|
Cytoreductive therapy before HSCT
Yes
|
25 Participants
n=30 Participants
|
22 Participants
n=27 Participants
|
47 Participants
n=57 Participants
|
|
Marrow Blasts at enrollment
|
13 Percent of participants
n=30 Participants
|
11 Percent of participants
n=27 Participants
|
12 Percent of participants
n=57 Participants
|
|
Donor Type
Matched Unrelated
|
24 Participants
n=30 Participants
|
18 Participants
n=27 Participants
|
42 Participants
n=57 Participants
|
|
Donor Type
Matched Sibling
|
6 Participants
n=30 Participants
|
9 Participants
n=27 Participants
|
15 Participants
n=57 Participants
|
|
Cytomegalovirus (CMV) Serology Status
Recipient +/ Donor +
|
4 Participants
n=30 Participants
|
6 Participants
n=27 Participants
|
10 Participants
n=57 Participants
|
|
Cytomegalovirus (CMV) Serology Status
Recipient +/ Donor -
|
9 Participants
n=30 Participants
|
6 Participants
n=27 Participants
|
15 Participants
n=57 Participants
|
|
Cytomegalovirus (CMV) Serology Status
Recipient -/ Donor +
|
4 Participants
n=30 Participants
|
5 Participants
n=27 Participants
|
9 Participants
n=57 Participants
|
|
Cytomegalovirus (CMV) Serology Status
Recipient -/ Donor -
|
13 Participants
n=30 Participants
|
10 Participants
n=27 Participants
|
23 Participants
n=57 Participants
|
|
Conditioning Regimen
Myeloablative Conditioning Busulfan 4 days/Fludarabine
|
15 Participants
n=30 Participants
|
15 Participants
n=27 Participants
|
30 Participants
n=57 Participants
|
|
Conditioning Regimen
Reduced Intensity Conditioning Busulfan 2 days/Fludarabine
|
15 Participants
n=30 Participants
|
12 Participants
n=27 Participants
|
27 Participants
n=57 Participants
|
|
Graft Source
Bone Marrow
|
2 Participants
n=30 Participants
|
2 Participants
n=27 Participants
|
4 Participants
n=57 Participants
|
|
Graft Source
Peripheral Blood
|
28 Participants
n=30 Participants
|
25 Participants
n=27 Participants
|
53 Participants
n=57 Participants
|
PRIMARY outcome
Timeframe: 18 monthsProgression-Free Survival (PFS) at 18 months after randomization. Progression-free survival is defined as time from randomization to progression of disease or death whichever occurs first. Patients with relapse/progressive disease who re-enter remission after vaccination or upon withdrawal of immune suppression alone will not be considered as having disease progression. The primary analysis will be performed using the modified intention-to-treat (ITT) principle, i.e., all transplanted and eligible patients who receive at least one vaccination will be included in the analysis according to the treatment arm they are randomized to. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Progression is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features is defined by either morphological evidence of acute leukemia or MDS consistent with pre-transplant features
Outcome measures
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
18-Month Progression Free Survival
|
53 Percentage
Interval 34.0 to 69.0
|
55 Percentage
Interval 35.0 to 72.0
|
SECONDARY outcome
Timeframe: 18 MonthsPercentage of participants experiencing grade 3 or higher non-hematologic or grade or higher hematologic adverse events evaluated by CTCAE v5.0.
Outcome measures
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Percentage of Participants Experiencing Grade 3 or Higher Non-Hematologic or Grade 4 or Higher Hematologic Adverse Events
|
3.33 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: 1 and 3 yearsPercentage of participants with acute and chronic graft-versus-host disease (GVHD). The time frame for the acute incidence is 1 year and for chronic is 3 years.Grading of aGVHD was derived by consensus grading (Przepiorka 1995). The aGVHD algorithm calculates the grade based on the organ (skin, GI and liver) stage and etiology/biopsy reported. Skin staging: Stage 1. \<25% rash; 2. 25-50%; 3. \>50%; 4. generalized erythroderma with bullae. GI staging: Stage 1. Diarrhea\>500ml/d or persistent nausea; 2. \>1000ml/d; 3. \>1500ml/d; 4. Large volume diarrhea and severe abdominal pain +- ileus. Liver staging: Stage 1. bilirubin 2-3mg/dl; 2. bili 3-6 mg/dl; 3. bili 6-15 mg/dl; 4. bili\>15mg/dl. Grade 4 is the worst outcome. Chronic GVHD is classified using the NIH Consensus Criteria. 8 organs will be scored on a 0-3 scale to reflect degree of cGVHD involvement 0 being none, 1 mild, 2 moderate 3 severe. Liver and pulmonary function test results will also be recorded. Severe is the worst outcome
Outcome measures
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Percentage of Participants Experiencing Acute and Chronic Graft-Versus-Host Disease
Grade 2-4 aGVHD @1yr
|
34 Percentage of participants
|
12 Percentage of participants
|
|
Percentage of Participants Experiencing Acute and Chronic Graft-Versus-Host Disease
Grade 3-4 aGVHD @1yr
|
16 Percentage of participants
|
0 Percentage of participants
|
|
Percentage of Participants Experiencing Acute and Chronic Graft-Versus-Host Disease
Chronic GVHD @3yrs
|
47 Percentage of participants
|
59 Percentage of participants
|
|
Percentage of Participants Experiencing Acute and Chronic Graft-Versus-Host Disease
Mod-severe cGVHD @3yrs
|
23 Percentage of participants
|
33 Percentage of participants
|
SECONDARY outcome
Timeframe: 18 MonthsPercentage of participants with relapse and/or non-relapse mortality at 18 months from registration.
Outcome measures
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Percentage of Participants With Relapse and/or Non-Relapse Mortality
Non-relapse Mortality
|
17 Percentage of participants
|
7.7 Percentage of participants
|
|
Percentage of Participants With Relapse and/or Non-Relapse Mortality
Relapse
|
30 Percentage of participants
|
37 Percentage of participants
|
SECONDARY outcome
Timeframe: 18 MonthAssessment of overall survival at 18 months. Participants alive at last contact are censored at last contact.
Outcome measures
| Measure |
GVAX
n=30 Participants
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 Participants
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
18-Month Overall Survival
|
63 Percentage of participants
|
59 Percentage of participants
|
Adverse Events
GVAX
Serious events: 1 serious events
Other events: 10 other events
Deaths: 14 deaths
Placebo
Serious events: 2 serious events
Other events: 4 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
GVAX
n=30 participants at risk
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 participants at risk
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
3.3%
1/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
0.00%
0/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Investigations
Blood bilirubin increased
|
3.3%
1/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
0.00%
0/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
Other adverse events
| Measure |
GVAX
n=30 participants at risk
GVAX vaccine
Participants in the GVAX vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
GVAX: GVAX vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
Placebo
n=27 participants at risk
Placebo vaccine
Participants in the placebo vaccine arm will undergo a conditioning regimen with busulfan and fludarabine prior to allogeneic hematopoietic stem cell transplant. Immediately after allogeneic hematopoietic stem cell transplant participants will start tacrolimus and methotrexate to prevent GVHD.
Conditioning regimen: In this study the condition regimen will include 2 chemotherapy drugs: busulfan (twice a day or four times a day for 4 days) and fludarabine (once daily for 4 days). Depending on participant's age, and other clinical factors, the transplant doctor will decide whether the participant will receive a higher or lower dose of busulfan.
Allogeneic Hematopoietic Stem Cell Transplant: Between 1-2 days after participant finishes the chemotherapy, the participant will receive the blood stem cell or marrow from their donor.
GVHD Prevention:
* Tacrolimus- This will be taken orally twice daily start 3 days before the transplant, and will continue for about 6-9 months.
* Methotrexate- This will be given a short intravenous infusion on days 1, 3, 6, and 11 after the transplant.
Placebo: Placebo vaccination will begin between 30 to 45 days following participant's transplant, provided participant meets vaccination initiation criteria.
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Erythema Multiforme
|
20.0%
6/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
0.00%
0/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
General disorders
Fatigue
|
3.3%
1/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Skin and subcutaneous tissue disorders
Skin Induration
|
16.7%
5/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
0.00%
0/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
13.3%
4/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/30 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
3.7%
1/27 • 18 Months
Patients were monitored for local and systemic adverse reactions with weekly to twice weekly examinations and laboratory studies during the study period. Acute graft-versus host disease (GVHD) was graded according to Keystone criteria.19 Non-GVHD adverse events were reported according to the National Cancer Institute Common Toxicity Criteria v.4 guidelines.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place