Clinical trial NCT03275636: Haploidentical Donor vs mMUD in Hematological Malignancies
Official title: A Randomized Controlled Trial Comparing Outcome After Hematopoietic Cell Transplantation From a Partially Matched Unrelated Versus Haploidentical Donor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: AML
ALL
MDS
Keywords: Haploidentical
mismatched unrelated donor
hematopoietic stem cell transplantation
donor comparison
Lead sponsor: DKMS gemeinnützige GmbH
Sponsor class: OTHER
First posted: 2017-09-07
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this trial is to compare the outcome after partially matched (single mismatch) unrelated donor transplantation with haploidentical transplantation in a randomized controlled setting.

Detailed description: For patients with an indication for allogeneic HCT, the search for a stem cell donor is a challenge. 20% of patients who need an allograft have an HLA-identical sibling available, and for approximately 70% of the remaining patients, a suitable, HLA-well-matched (10/10), unrelated volunteer can be found. For the remaining patients, partially matched (single mismatch) unrelated donors or haploidentical donors are alternative options.

Recently published retrospective single center and registry studies suggest comparable outcomes for HCT from unrelated donors matched at HLA -A, -B, -C, and -DRB1 and haploidentical donors. The number of haploidentical HCT evaluated in these studies was still relatively small and a selection bias for the retrospective comparisons cannot be excluded.

The goal of this trial is to evaluate overall survival of patients with high-risk AML, ALL or MDS after partially matched unrelated or haploidentical donor transplantation..

Eligibility criteria: Inclusion criteria

1. Eligible diagnoses are listed below:

   AML with adverse risk genetic abnormalities (according to the ELN guidelines)1. AML with intermediate genetic abnormalities (according to ELN guidelines) either in first complete remission, after relapse, or by chemotherapy-refractory disease.

   AML with favourable genetic abnormalities (according to ELN guidelines) after relapse or by chemotherapy-refractory disease, except APL.

   AML with undefined genetic risk classification after relapse or with chemotherapy-refractory disease.

   AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN guidelines) are present.

   Therapy-related myeloid neoplasia except if favorable genetic abnormalities (according to ELN guidelines) are present.

   MDS with high risk or very high risk disease (according to the IPSS-R score)2.

   First CR of high-risk ALL, defined by one or more of these:
   * Early or mature T-ALL (CD1a negative).
   * Pro B-ALL with t(4v;11); KMT2A-rearrangements.
   * Presence of BCR-ABL and/or t(9;22).
   * Persistence of minimal residual disease after the second induction course. ALL with or without complete remission after salvage therapy following poor response to induction therapy.

   ALL after haematological or molecular relapse.
2. Fit for transplant according to physician judgement.
3. No history of cardiac disease and absence of active symptoms, otherwise, documented left ventricular ejection fraction ≥40%.
4. No history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) ≥40% or FEV1/FVC ≥ 50% despite appropriate treatment
5. Availability of ≥1 unrelated donor with a single allele or antigen mismatch at HLA-A, -B, -C, or -DRB1 and no concurrent DQB1 mismatch (9/10) shown by confirmatory typing.
6. Availability of at least one haploidentical donor meeting the following criteria:

Donor is a biologic parent / child of the patient, or haploidentity has been confirmed for patient's relatives by HLA-Typing.

The donor has expressed his/her will to donate and has no contraindications against a stem cell donation by medical history.

Donor age is ≥18 years and ≤75 years.

Exclusion criteria

1. Relapse or graft failure after a first allogeneic transplantation.
2. Thymic ALL in first complete remission.
3. Severe organ dysfunction defined by either of the following three criteria:

   Patients who receive supplementary continuous oxygen. Serum bilirubin \>1.5 x ULN (if not considered Gilbert-Syndrome) or ASAT/ALAT \>5 x ULN.

   Estimated Glomerular Filtration Rate (GFR) \< 40 mL/min
4. Uncontrolled infection at the time of enrollment.
5. Pregnant or breast-feeding women.
6. An HLA-identical sibling donor or 8/8 (HLA-A, -B, -C, or -DRB1) matched unrelated donor is available and suitable to donate prior to randomization.
7. Men unable or unwilling to use adequate contraception methods from enrollment to minimum of six months after the last dose of chemotherapy.
8. Women of childbearing potential except those who fulfill the following criteria: Post-menopausal or post-operative or continuous and correct application of a contraception method with a Pearl Index \<1% or sexual abstinence or vasectomy of the sexual partner.
9. Simultaneous participation in another clinical trial.

Primary outcomes:
measure: Overall survival
timeFrame: 2 years
Secondary outcomes:
measure: Engraftment rate
timeFrame: day 56
measure: Immune-reconstitution rate
timeFrame: day56
measure: Infections
timeFrame: 2 months after HCT
measure: Event Free Survival
timeFrame: 1 year
measure: Graft vs Host Disease
timeFrame: 1 year
measure: Graft vs Host Disease-free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg Nord
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: Universtitätsklinikum Dresden
name: Johannes Schetelig, Prof Dr med
role: STUDY_CHAIR
References: