Clinical trial NCT04232241: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia in Remission
Acute Lymphoblastic Leukemia in Remission
Myelodysplastic Syndromes
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
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: GKM Gesellschaft für Therapieforschung mbH
name: Staburo GmbH
First posted: 2020-01-18
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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%.

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.

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.

Primary outcomes:
measure: Relapse incidence at two years between both arms
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival at two years between both arms
timeFrame: 2 years
measure: Overall survival for all patients assigned to one of the two treatment arms as time to event endpoint
timeFrame: through study completion, an average of two yeras
measure: Comparison of GVHD/relapse-free survival as Composite endpoint in both arms
timeFrame: Starting at day +30 (+/- 3 d) to 24 months (+/- 1 mo) after allogenic stem cell transplantation (SCT)
measure: Comparison of non-relapsed mortality (NRM) at 1 and 2 years after allogeneic SCT in both arms
timeFrame: At 1 and 2 years after allogeneic SCT
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
timeFrame: On day +100 and 1 year (max grade) after allogeneic SCT
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
timeFrame: At 1 and 2 years after allogeneic SCT
measure: Comparison of toxicity of both regimens scored according to the current version of the NCI CTCAE between both arms
timeFrame: through study completion, an average of two yeras
measure: Comparison of immune reconstitution between both arms
timeFrame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
measure: Comparison of full donor chimerism between both arms
timeFrame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT
measure: Evaluation of Sorror Risk Score on outcome after allogeneic SCT
timeFrame: At baseline
measure: Comparison of QOL (FACT-BMT) before and after transplantation at + 100 days, 6 months, 1 year, 2 years between both arms
timeFrame: At day 100, 6 months, 1 year and 2 years after allogenic SCT
Other outcomes:
measure: Scientific Endpoint (optional)
timeFrame: 2 years
measure: Scientific Endpoint (optional)
timeFrame: 2 years
Locations:
city: Graz
country: Austria
facility: LKH-Univ. Klinikum Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Medizinische Universität Wien, Universitätsklinik für Innere Medizin I Einrichtung für Stammzelltransplantation KMT
city: Prague
country: Czechia
facility: Institute of Hematology and Blood Transfusion
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Düsseldorf
country: Germany
facility: University Hospital Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt am Main | Medizinische Klinik II
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig Dep. Innere Medizin, Neurologie und Dermatologie Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: St. Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital Clínico y Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico de La Fe
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
name: Nicolaus Kröger, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanz J, Galimard JE, Labopin M, Afanasyev B, Sergeevich MI, Angelucci E, Kroger N, Koc Y, Ciceri F, Diez-Martin JL, Arat M, Sica S, Rovira M, Aljurf M, Tischer J, Savani B, Ruggeri A, Nagler A, Mohty M. Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT. J Hematol Oncol. 2021 May 28;14(1):84. doi: 10.1186/s13045-021-01094-2.