Matched Unrelated vs. Haploidentical Donor for Allogeneic Stem Cell Transplantation in Patients With Acute Leukemia

Myelodysplastic Syndromes Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04232241
• Other study ID #: HaploMUDStudy
• Status: Recruiting
• Phase: Phase 2
• Start date: November 14, 2019
• Est. completion date: November 2024

Study information

• Verified date: October 2021
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: Nicolaus Kröger, Prof. Dr.
• Phone: +49 (0) 40 7410 55864
• Email: n.kroeger[@]uke.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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%.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: November 2024
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia in Remission
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• Allogeneic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation

Locations

Country	Name	City	State
Austria	LKH-Univ. Klinikum Graz	Graz
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT	Wien
Czechia	Institute of Hematology and Blood Transfusion	Prague
Finland	Turku University Central Hospital	Turku
Germany	University Hospital Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Frankfurt am Main | Medizinische Klinik II	Frankfurt
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie	Leipzig
Germany	Universitätsklinikum Münster	Münster
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	ASST Papa Giovanni XXIII	Bergamo
Russian Federation	Pavlov First Saint Petersburg State Medical University	St. Petersburg
Spain	Hospital Universitari Germans Trias I Pujol	Badalona
Spain	Hospital Clínico y Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario y Politécnico de La Fe	Valencia

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Clinical Trial Center North (CTC North GmbH & Co. KG), DKMS Stiftung Leben Spenden

Countries where clinical trial is conducted

Austria,  Czechia,  Finland,  Germany,  Italy,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Scientific Endpoint (optional)	Comparison of relapse incidence at two years between MRD positive and negative patients in both arms	2 years
Other	Scientific Endpoint (optional)	Comparison of overall survival at two years between MRD positive and negative patients in both arms	2 years
Primary	Relapse incidence at two years between both arms	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.	2 years
Secondary	Overall survival at two years between both arms	The overall survival at two years between both arms will be presented with Kaplan-Meier's estimates of survival.	2 years
Secondary	Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint	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.	through study completion, an average of two yeras
Secondary	Comparison of GVHD/relapse-free survival as Composite endpoint in both arms	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.	Starting at day +30 (+/- 3 d) to 24 months (+/- 1 mo) after allogenic stem cell transplantation (SCT)
Secondary	Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic SCT in both arms	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	At 1 and 2 years after allogeneic SCT
Secondary	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	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.	On day +100 and 1 year (max grade) after allogeneic SCT
Secondary	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	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.	At 1 and 2 years after allogeneic SCT
Secondary	Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms	Safety will be analyzed with frequency of patients with AEs as described above.	through study completion, an average of two yeras
Secondary	Comparison of immune reconstitution between both arms	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.	At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
Secondary	Comparison of full donor chimerism between both arms	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.	At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
Secondary	Evaluation of Sorror Risk Score on outcome after allogeneic SCT	Comorbidity score after Sorror will be assessed prior to randomization and outcome in both arms will be analyzed according the pre-transplant Sorror score.	At baseline
Secondary	Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms	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.	At day 100, 6 months, 1 year and 2 years after allogenic SCT