Clinical Trials /

Haploidentical Donor vs mMUD in Hematological Malignancies

NCT03275636

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Therapy-Related Myeloid Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: DKMS-16-01
  • SECONDARY ID: 2015-005399-12
  • NCT ID: NCT03275636

Conditions

  • AML
  • ALL
  • MDS

Interventions

DrugSynonymsArms
Peripheral blood stem cellsPBSCHaploidentical donor

Purpose

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..
    

Trial Arms

NameTypeDescriptionInterventions
Haploidentical donorExperimental
  • Peripheral blood stem cells
partially matched unrelated donorExperimentalunrelated 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
  • Peripheral blood stem cells

Eligibility Criteria

        Inclusion Criteria:

          1. Eligible diagnoses are listed below:

               -  AML with adverse risk genetic abnormalities (according to the ELN guidelines)

               -  AML with intermediate genetic abnormalities (according to ELN guidelines) 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)

               -  First CR of high-risk ALL (classification of ALL according to GMALL3), defined by
                  one or more of these:

                    -  Phenotype (pro B-ALL, early T-ALL, or mature T-ALL).

                    -  High-risk genetic markers (t(4;11)/ALL1-AF4 or t(9;22)/BCR-ABL).

                    -  WBC count > 30 GPt/L at diagnosis.

                    -  Delayed CR (no CR on day 26 after first induction course).

                    -  Persistence of minimal residual disease after the second induction course.

               -  ALL in second complete remission.

          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

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:2 years
Safety Issue:
Description:Overall survival calculated from the time of randomization will be the primary endpoint of this trial. Death from any reason will be considered as event.

Secondary Outcome Measures

Measure:engraftment rate
Time Frame:day 56
Safety Issue:
Description:
Measure:immune-reconstitution rate
Time Frame:day56
Safety Issue:
Description:
Measure:Severe infections rate
Time Frame:2 months after HCT
Safety Issue:
Description:
Measure:Event Free Survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Graft vs Host Disease rate
Time Frame:1 year
Safety Issue:
Description:
Measure:Graft vs Host Disease-free survival rate
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:DKMS gemeinnützige GmbH

Trial Keywords

  • Haploidentical
  • mismatched unrelated donor
  • hematopoietic stem cell transplantation
  • donor comparison

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