NCT02440464 · OUTCOME
Percentage of Participants With Best Response to Treatment After Randomization
Allogeneic Hematopoietic Stem Cell Transplantation With Ixazomib for High Risk Multiple Myeloma (BMT CTN 1302) · Source last updated 2023-01-04
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- COUNT_OF_PARTICIPANTS
- Unit
- Participants
- Interval / dispersion
- Not reported
- Time frame
- 2 years post-transplant
What was measured
Response was assessed using the International Uniform Response Criteria. Best response is the best of all the disease response status at each assessment time point after randomization. The order from best to worst is: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). All disease classifications are relative to the patient's disease status prior to allogeneic transplant (i.e. study entry). This outcome was compared between treatment groups using all response data up to 2 years post-transplant. These response data were summarized separately for patients in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization. Within each group (in sCR/CR vs not in sCR/CR at randomization), best response to treatment was compared between treatment groups using a Fisher's Exact test instead of a chi-square test because of the small sample size.
Analysis population: All randomized participants were included in the analysis. Participants were divided into those in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization.
Groups in this outcome
Ixazomib Maintenance
Allogeneic HSCT and Fludarabine/Melphalan/Bortezomib conditioning followed by Ixazomib maintenance
Allogeneic HSCT: Eligible patients with a Human Leukocyte Antigen (HLA)-matched related or unrelated donor will undergo allogeneic hematopoietic stem cell transplant at Day 0. For GVHD prophylaxis, patients will be given Tacrolimus from Day -3 until at least 6 months following initiation, at an intravenous daily dose of 0.015 mg/kg. This will be combined with an intravenous administration of Methotrexate at 5 mg/m2 on Days +1, +3, +6, and +11.
Fludarabine: Patients will receive conditioning treatment before and after HSCT. Fludarabine will be given at 30 mg/m2 intravenously on Day -6 through Day -3.
Melphalan: Melphalan will be given at 70 mg/m2 intravenously on Days -4 and -3.
Bortezomib: Bortezomib will be administered at 1.3 mg/m2 intravenously on Day -3.
Ixazomib: Between 60 and 120 days following HSCT, patients randomized to the experimental arm will receive Ixazomib maintenance. Maintenance will begin at 3-mg oral doses on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule, following successful completion of 3 cycles at the previous dosage, for a total of 12 cycles.
Placebo
Allogeneic HSCT and Fludarabine/Melphalan/Bortezomib conditioning followed by placebo maintenance.
Allogeneic HSCT: Eligible patients with a Human Leukocyte Antigen (HLA)-matched related or unrelated donor will undergo allogeneic hematopoietic stem cell transplant at Day 0. For GVHD prophylaxis, patients will be given Tacrolimus from Day -3 until at least 6 months following initiation, at an intravenous daily dose of 0.015 mg/kg. This will be combined with an intravenous administration of Methotrexate at 5 mg/m2 on Days +1, +3, +6, and +11.
Fludarabine: Patients will receive conditioning treatment before and after HSCT. Fludarabine will be given at 30 mg/m2 intravenously on Day -6 through Day -3.
Melphalan: Melphalan will be given at 70 mg/m2 intravenously on Days -4 and -3.
Bortezomib: Bortezomib will be administered at 1.3 mg/m2 intravenously on Day -3.
Placebo: Between 60 and 120 days following HSCT, patients randomized to the control group will be given 3 mg of placebo orally on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule following successful completion of 3 cycles of placebo maintenance at the 3-mg dose. This will continue for a total of 12 cycles.
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 |
|---|
| Ixazomib Maintenance | 21 |
|---|
| Placebo | 22 |
|---|
Reported measurements
Participants in sCR/CR at Randomization
Analysis denominator · Participants
| Group | Source count |
|---|
| Ixazomib Maintenance | 9 |
|---|
| Placebo | 11 |
|---|
Stringent Complete Response (sCR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 6 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 5 | Not reported | Not reported | Not reported | Not reported |
|---|
Complete Response (CR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 2 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 4 | Not reported | Not reported | Not reported | Not reported |
|---|
Very Good Partial Response (VGPR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 1 | Not reported | Not reported | Not reported | Not reported |
|---|
Partial Response (PR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
Stable Disease (SD)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
Progressive Disease (PD)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 1 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 1 | Not reported | Not reported | Not reported | Not reported |
|---|
Participants Not in sCR/CR at Randomization
Analysis denominator · Participants
| Group | Source count |
|---|
| Ixazomib Maintenance | 12 |
|---|
| Placebo | 11 |
|---|
Stringent Complete Response (sCR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 3 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 4 | Not reported | Not reported | Not reported | Not reported |
|---|
Complete Response (CR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 2 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 3 | Not reported | Not reported | Not reported | Not reported |
|---|
Very Good Partial Response (VGPR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 4 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 4 | Not reported | Not reported | Not reported | Not reported |
|---|
Partial Response (PR)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 2 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
Stable Disease (SD)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
Progressive Disease (PD)
Values in Participants · Interval/dispersion: Not reported| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Ixazomib Maintenance | 1 | Not reported | Not reported | Not reported | Not reported |
|---|
| Placebo | 0 | Not reported | Not reported | Not reported | Not reported |
|---|
Source statistical analyses
Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.
- group Description
- Participants in sCR/CR at Randomization
- non Inferiority Comment
- The null hypothesis is that there is no difference in the proportions of participants in the best response to treatment categories between the Ixazomib and Placebo arms during 2 years post-transplant among participants in sCR/CR at randomization. These proportions were compared using Fisher's Exact test.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.890
- statistical Comment
- Statistical significance was determined using a pre-specified one-sided threshold of 0.05.
- statistical Method
- Fisher Exact
- group Description
- The null hypothesis is that there is no difference in the proportions of participants in the best response to treatment categories between the Ixazomib and Placebo arms during 2 years post-transplant among participants not in sCR/CR at randomization. These proportions were compared using Fisher's Exact test.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.754
- p Value Comment
- Statistical significance was determined using a pre-specified one-sided threshold of 0.05.
- statistical Method
- Fisher Exact
Complete source fields
- analyses
- group Description
- Participants in sCR/CR at Randomization
- non Inferiority Comment
- The null hypothesis is that there is no difference in the proportions of participants in the best response to treatment categories between the Ixazomib and Placebo arms during 2 years post-transplant among participants in sCR/CR at randomization. These proportions were compared using Fisher's Exact test.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.890
- statistical Comment
- Statistical significance was determined using a pre-specified one-sided threshold of 0.05.
- statistical Method
- Fisher Exact
- group Description
- The null hypothesis is that there is no difference in the proportions of participants in the best response to treatment categories between the Ixazomib and Placebo arms during 2 years post-transplant among participants not in sCR/CR at randomization. These proportions were compared using Fisher's Exact test.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.754
- p Value Comment
- Statistical significance was determined using a pre-specified one-sided threshold of 0.05.
- statistical Method
- Fisher Exact
- classes
- categories
- measurements
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 5
- title
- Stringent Complete Response (sCR)
- measurements
- group Id
- OG000
- value
- 2
- group Id
- OG001
- value
- 4
- title
- Complete Response (CR)
- measurements
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 1
- title
- Very Good Partial Response (VGPR)
- measurements
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- title
- Partial Response (PR)
- measurements
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- title
- Stable Disease (SD)
- measurements
- group Id
- OG000
- value
- 1
- group Id
- OG001
- value
- 1
- title
- Progressive Disease (PD)
- denoms
- counts
- group Id
- OG000
- value
- 9
- group Id
- OG001
- value
- 11
- units
- Participants
- title
- Participants in sCR/CR at Randomization
- categories
- measurements
- group Id
- OG000
- value
- 3
- group Id
- OG001
- value
- 4
- title
- Stringent Complete Response (sCR)
- measurements
- group Id
- OG000
- value
- 2
- group Id
- OG001
- value
- 3
- title
- Complete Response (CR)
- measurements
- group Id
- OG000
- value
- 4
- group Id
- OG001
- value
- 4
- title
- Very Good Partial Response (VGPR)
- measurements
- group Id
- OG000
- value
- 2
- group Id
- OG001
- value
- 0
- title
- Partial Response (PR)
- measurements
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 0
- title
- Stable Disease (SD)
- measurements
- group Id
- OG000
- value
- 1
- group Id
- OG001
- value
- 0
- title
- Progressive Disease (PD)
- denoms
- counts
- group Id
- OG000
- value
- 12
- group Id
- OG001
- value
- 11
- units
- Participants
- title
- Participants Not in sCR/CR at Randomization
- denoms
- counts
- group Id
- OG000
- value
- 21
- group Id
- OG001
- value
- 22
- units
- Participants
- description
- Response was assessed using the International Uniform Response Criteria. Best response is the best of all the disease response status at each assessment time point after randomization. The order from best to worst is: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Stable Disease (SD), and Progressive Disease (PD). All disease classifications are relative to the patient's disease status prior to allogeneic transplant (i.e. study entry). This outcome was compared between treatment groups using all response data up to 2 years post-transplant. These response data were summarized separately for patients in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization. Within each group (in sCR/CR vs not in sCR/CR at randomization), best response to treatment was compared between treatment groups using a Fisher's Exact test instead of a chi-square test because of the small sample size.
- groups
- description
- Allogeneic HSCT and Fludarabine/Melphalan/Bortezomib conditioning followed by Ixazomib maintenance
Allogeneic HSCT: Eligible patients with a Human Leukocyte Antigen (HLA)-matched related or unrelated donor will undergo allogeneic hematopoietic stem cell transplant at Day 0. For GVHD prophylaxis, patients will be given Tacrolimus from Day -3 until at least 6 months following initiation, at an intravenous daily dose of 0.015 mg/kg. This will be combined with an intravenous administration of Methotrexate at 5 mg/m2 on Days +1, +3, +6, and +11.
Fludarabine: Patients will receive conditioning treatment before and after HSCT. Fludarabine will be given at 30 mg/m2 intravenously on Day -6 through Day -3.
Melphalan: Melphalan will be given at 70 mg/m2 intravenously on Days -4 and -3.
Bortezomib: Bortezomib will be administered at 1.3 mg/m2 intravenously on Day -3.
Ixazomib: Between 60 and 120 days following HSCT, patients randomized to the experimental arm will receive Ixazomib maintenance. Maintenance will begin at 3-mg oral doses on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule, following successful completion of 3 cycles at the previous dosage, for a total of 12 cycles.
- id
- OG000
- title
- Ixazomib Maintenance
- description
- Allogeneic HSCT and Fludarabine/Melphalan/Bortezomib conditioning followed by placebo maintenance.
Allogeneic HSCT: Eligible patients with a Human Leukocyte Antigen (HLA)-matched related or unrelated donor will undergo allogeneic hematopoietic stem cell transplant at Day 0. For GVHD prophylaxis, patients will be given Tacrolimus from Day -3 until at least 6 months following initiation, at an intravenous daily dose of 0.015 mg/kg. This will be combined with an intravenous administration of Methotrexate at 5 mg/m2 on Days +1, +3, +6, and +11.
Fludarabine: Patients will receive conditioning treatment before and after HSCT. Fludarabine will be given at 30 mg/m2 intravenously on Day -6 through Day -3.
Melphalan: Melphalan will be given at 70 mg/m2 intravenously on Days -4 and -3.
Bortezomib: Bortezomib will be administered at 1.3 mg/m2 intravenously on Day -3.
Placebo: Between 60 and 120 days following HSCT, patients randomized to the control group will be given 3 mg of placebo orally on Days 1, 8, and 15 of a 28-day cycle. This will increase to 4-mg doses on the same cycle schedule following successful completion of 3 cycles of placebo maintenance at the 3-mg dose. This will continue for a total of 12 cycles.
- id
- OG001
- title
- Placebo
- param Type
- COUNT_OF_PARTICIPANTS
- population Description
- All randomized participants were included in the analysis. Participants were divided into those in sCR/CR at the time of randomization vs. those who were not in sCR/CR at the time of randomization.
- reporting Status
- POSTED
- time Frame
- 2 years post-transplant
- title
- Percentage of Participants With Best Response to Treatment After Randomization
- type
- SECONDARY
- unit Of Measure
- Participants
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Preserved source evidence · Not medical advice
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