Description:
Primary objective of this open label, two-arm, multicenter, multinational, randomized trial
is to compare anti-leukemic activity of allogeneic stem cell transplantation for patients
with acute leukemia in complete remission between a 10/10 HLA matched unrelated donor and a
haploidentical donor.
The hypothesis: Haploidentical stem cell transplantation with post cyclophosphamide induces a
stronger anti-leukemic activity in comparison to 10/10 HLA matched unrelated donor and
reduces the risk of relapse at 2 years after stem cell transplantation by 10%.
Title
- Brief Title: Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia
- Official Title: Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia With Identical GVHD Prophylaxis - A Randomized Prospective European Trial.
Clinical Trial IDs
- ORG STUDY ID:
HaploMUDStudy
- NCT ID:
NCT04232241
Conditions
- Acute Myeloid Leukemia in Remission
- Acute Lymphoblastic Leukemia in Remission
- Myelodysplastic Syndromes
Interventions
| Drug | Synonyms | Arms |
|---|
| Allogeneic Stem Cell Transplantation | | Treatment A |
Purpose
Primary objective of this open label, two-arm, multicenter, multinational, randomized trial
is to compare anti-leukemic activity of allogeneic stem cell transplantation for patients
with acute leukemia in complete remission between a 10/10 HLA matched unrelated donor and a
haploidentical donor.
The hypothesis: Haploidentical stem cell transplantation with post cyclophosphamide induces a
stronger anti-leukemic activity in comparison to 10/10 HLA matched unrelated donor and
reduces the risk of relapse at 2 years after stem cell transplantation by 10%.
Detailed Description
Secondary objectives are to assess and compare the safety and efficacy of study treatments
therapy in both study arms on non-relapse mortality (NRM), relapse-free survival (RFS),
Overall survival (OS), QOL, toxicity, development of acute and chronic GvDH as well as
engraftment and chimerism and impact of measurable residual disease.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Treatment A | Active Comparator | Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor | - Allogeneic Stem Cell Transplantation
|
| Treatment B | Experimental | Allogeneic stem cell transplantation from haploidentical donor | - Allogeneic Stem Cell Transplantation
|
Eligibility Criteria
Inclusion Criteria
1. Acute Myeloid Leukemia (AML) intermediate or high risk according to ELN or Acute
Lymphoblastic Leukemia (ALL) high risk according to ESMO guidelines in 1. CR or
AML/ALL in 2. CR, or high risk MDS (according to IPSS-R) in 1. CR or 2. CR.
2. Patients age: 18 - 70 years at time of inclusion (female and male).
3. Patients understand and voluntarily sign an informed consent form.
4. ECOG ≤ 2.
5. 10/10 HLA-matched unrelated donor and haploidentical (≥ 5/10 and ≤ 8/10 HLA) relative
matched donor available at least 4 weeks after completion of induction and/or
consolidation therapy.
6. Females/Males who agree to comply with the applicable contraceptive requirements of
the protocol.
Exclusion Criteria
1. Severe renal, hepatic, pulmonary or cardiac disease, such as:
- total bilirubin, SGPT or SGOT > 3 times upper the normal level
- left ventricular ejection fraction < 30 %
- creatinine clearance < 30 ml/min
- DLCO < 35 % and/or receiving supplementary continuous oxygen
2. Positive serology for HIV.
3. Pregnant or lactating women (positive serum pregnancy test).
4. Age < 18 and ≥ 71 years.
5. Uncontrolled invasive fungal infection at time of screening (baseline).
6. Serious psychiatric or psychological disorders.
7. Participation in another study with ongoing use of unlicensed investigational product
from 28 days before study enrollment.
8. Uncontrolled severe autoimmune disease or uncontrolled other malignancy.
9. Availability of an HLA-identical sibling as donor source.
| Maximum Eligible Age: | 70 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Relapse incidence at two years between both arms |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | The primary efficacy endpoint will be analyzed using cumulative incidence estimation to assess the subdistribution hazard rates for both treatment groups at two years after accounting for competing risk events. |
Secondary Outcome Measures
| Measure: | Overall survival at two years between both arms |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | The overall survival at two years between both arms will be presented with Kaplan-Meier's estimates of survival. |
| Measure: | Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint |
| Time Frame: | through study completion, an average of two yeras |
| Safety Issue: | |
| Description: | The overall survival for all patients will be presented with Kaplan-Meier curve. To compare the survival distributions between two arms, log-rank test will be performed, and two-sided p-values will be presented.
If applicable, Cox regression model stratified by the types of leukemia, types of complete remission and conditioning will be performed as sensitivity analysis. |
| Measure: | Comparison of GVHD/relapse-free survival as Composite endpoint in both arms |
| Time Frame: | Starting at day +30 (+/- 3 d) to 24 months (+/- 1 mo) after allogenic stem cell transplantation (SCT) |
| Safety Issue: | |
| Description: | The rate of composite endpoint in both arms will be analyzed with the same methods as for the overall survival at two years between both arms. |
| Measure: | Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic SCT in both arms |
| Time Frame: | At 1 and 2 years after allogeneic SCT |
| Safety Issue: | |
| Description: | Due to the existence of competing risk events (persisting disease and relapse), NRM of each arm at 1 and 2 years after allogeneic SCT will be analyzed with the same methods as for the primary endpoint |
| Measure: | Comparison of acute graft-versus-host disease (aGVHD) on day +100 and 1 year (max grade) after allogeneic SCT according to the Glucksberg scale revised by Przepiorka et al. between both arms |
| Time Frame: | On day +100 and 1 year (max grade) after allogeneic SCT |
| Safety Issue: | |
| Description: | For each time point, the frequency and percentage of aGVHD (maximum grade) of each arm will be presented. To compare the difference between both arms, logistic regression adjusted for covariates and stratification factors will be performed. |
| Measure: | Comparison of chronic graft-versus-host disease (cGVHD) according to the NIH consensus criteria of Jagasia et al. at 1 and 2 years after allogeneic SCT between both arms |
| Time Frame: | At 1 and 2 years after allogeneic SCT |
| Safety Issue: | |
| Description: | For each time point, the frequency and percentage of cGVHD of each arm will be presented. To compare the difference between both arms, logistic regression adjusted for the stratification factors will be performed. |
| Measure: | Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms |
| Time Frame: | through study completion, an average of two yeras |
| Safety Issue: | |
| Description: | Safety will be analyzed with frequency of patients with AEs as described above. |
| Measure: | Comparison of immune reconstitution between both arms |
| Time Frame: | At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT |
| Safety Issue: | |
| Description: | Frequency and percentage of patients having immune reconstitution in two arms will be provided. For the comparison between two arms, logistic regression adjusted for the stratification factors will be performed. |
| Measure: | Comparison of full donor chimerism between both arms |
| Time Frame: | At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT |
| Safety Issue: | |
| Description: | Frequency and percentage of patients having full donor chimerism in two arms will be provided. For the comparison between two arms, logistic regression adjusted for the stratification factors will be performed. |
| Measure: | Evaluation of Sorror Risk Score on outcome after allogeneic SCT |
| Time Frame: | At baseline |
| Safety Issue: | |
| Description: | Comorbidity score after Sorror will be assessed prior to randomization and outcome in both arms will be analyzed according the pre-transplant Sorror score. |
| Measure: | Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms |
| Time Frame: | At day 100, 6 months, 1 year and 2 years after allogenic SCT |
| Safety Issue: | |
| Description: | The means of change in scores at each time point (day 100, 6 months, 1 year and 2 years after transplantation respectively) from baseline and the confidence intervals of each arm will be presented. To compare the difference in QOL scores between both arms, logistic regression adjusted for covariates and stratification factors will be performed for each time point. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Universitätsklinikum Hamburg-Eppendorf |
Trial Keywords
- Acute Myeloid Leukemia
- Acute Lymphoblastic Leukemia
- Myelodysplastic Syndromes
- Allogeneic Stem Cell Transplantation
- Matched Unrelated Allogeneic Stem Cell Transplantation
- Haploidentical Allogeneic Stem Cell Transplantation
- anti-leukemic activity
- Cyclophosphamide as GVHD prophylaxis
Last Updated
April 27, 2021
