Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04232241
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
DKMS Stiftung Leben Spenden
Clinical Trial Center North (CTC North GmbH & Co. KG)
Information provided by (Responsible Party):
Universitätsklinikum Hamburg-Eppendorf

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%.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia in Remission Acute Lymphoblastic Leukemia in Remission Myelodysplastic Syndromes Drug: Allogeneic Stem Cell Transplantation Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : November 14, 2019
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
Active Comparator: Treatment A
Allogeneic stem cell transplantation from 10/10 HLA matched unrelated donor
Drug: Allogeneic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation

Experimental: Treatment B
Allogeneic stem cell transplantation from haploidentical donor
Drug: Allogeneic Stem Cell Transplantation
Allogeneic Stem Cell Transplantation




Primary Outcome Measures :
  1. Relapse incidence at two years between both arms [ Time Frame: 2 years ]
    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 :
  1. Overall survival at two years between both arms [ Time Frame: 2 years ]
    The overall survival at two years between both arms will be presented with Kaplan-Meier's estimates of survival.

  2. 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 ]

    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.


  3. 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) ]
    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.

  4. 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 ]
    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

  5. 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 ]
    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.

  6. 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 ]
    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.

  7. 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 will be analyzed with frequency of patients with AEs as described above.

  8. Comparison of immune reconstitution between both arms [ Time Frame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT ]
    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.

  9. Comparison of full donor chimerism between both arms [ Time Frame: At day 30, 100, 6 months, 1 year and 2 years after allogenic SCT ]
    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.

  10. Evaluation of Sorror Risk Score on outcome after allogeneic SCT [ Time Frame: At baseline ]
    Comorbidity score after Sorror will be assessed prior to randomization and outcome in both arms will be analyzed according the pre-transplant Sorror score.

  11. 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 ]
    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.


Other Outcome Measures:
  1. Scientific Endpoint (optional) [ Time Frame: 2 years ]
    Comparison of relapse incidence at two years between MRD positive and negative patients in both arms

  2. Scientific Endpoint (optional) [ Time Frame: 2 years ]
    Comparison of overall survival at two years between MRD positive and negative patients in both arms



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04232241


Contacts
Layout table for location contacts
Contact: Nicolaus Kröger, Prof. Dr. +49 (0) 40 7410 55864 n.kroeger@uke.de
Contact: Frauke Bach, Dr. +49 (0) 40 7410 23182 f.bach@uke.de

Locations
Layout table for location information
Austria
LKH-Univ. Klinikum Graz Not yet recruiting
Graz, Austria, 8036
Contact: Hildegard Greinix, Prof. Dr.       Hildegard.Greinix@klinikum-graz.at   
Principal Investigator: Hildegard Greinix, Prof. Dr.         
Sub-Investigator: Heinz Sill, Prof. Dr.         
Finland
Turku University Central Hospital Not yet recruiting
Turku, Finland, 20521
Contact: Maija Itälä-Remes, Prof. Dr.       maija.itala-remes@tyks.fi   
Principal Investigator: Maija Itälä-Remes, Prof. Dr.         
Sub-Investigator: Urpu Salmenniemi, Prof. Dr.         
Germany
University Hospital Düsseldorf Not yet recruiting
Düsseldorf, Germany, 40225
Contact: Guido Kobbe, Prof. Dr.       kobbe@med.uni-duesseldorf.de   
Principal Investigator: Guido Kobbe, Prof. Dr.         
Sub-Investigator: Thomas Schröder, Dr.         
Universitätsklinikum Essen Not yet recruiting
Essen, Germany, 45122
Contact: Dietrich W. Beelen, Prof. Dr.       dietrich.beelen@uk-essen.de   
Principal Investigator: Dietrich W. Beelen, Prof. Dr.         
Sub-Investigator: Rudolf Trenschel, Dr.         
Universitätsklinikum Freiburg Not yet recruiting
Freiburg, Germany, 79106
Contact: Jürgen Finke, Prof. Dr.       juergen.finke@uniklinik-freiburg.de   
Principal Investigator: Jürgen Finke, Prof. Dr.         
Sub-Investigator: Hartmut Bertz, Prof. Dr.         
Universitätsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Nicolaus Kroeger, Prof. Dr.    +49 (0) 40 7410 55864    n.kroeger@uke.de   
Principal Investigator: Nicolaus Kroeger, Prof. Dr.         
Sub-Investigator: Christine Wolschke, Dr.         
Medizinische Hochschule Hannover Recruiting
Hannover, Germany, 30625
Contact: Matthias Eder, Prof. Dr.       eder.matthias@mh-hannover.de   
Principal Investigator: Matthias Eder, Prof. Dr.         
Sub-Investigator: Gernot Beutel, Dr.         
Universitätsklinikum Münster Recruiting
Münster, Germany, 48149
Contact: Matthias Stelljes, Prof. Dr.       Matthias.Stelljes@ukmuenster.de   
Principal Investigator: Matthias Stelljes, Prof. Dr.         
Sub-Investigator: Jan-Henrik Mikesch, Dr.         
Russian Federation
Pavlov First Saint Petersburg State Medical University Not yet recruiting
Saint Petersburg, Russian Federation, 197022
Contact: Boris Afanasyev, Prof. Dr.       bmt-director@1spbgmu.ru   
Principal Investigator: Boris Afanasyev, Prof. Dr.         
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
DKMS Stiftung Leben Spenden
Clinical Trial Center North (CTC North GmbH & Co. KG)
Investigators
Layout table for investigator information
Principal Investigator: Nicolaus Kröger, Prof. Dr. University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation
Layout table for additonal information
Responsible Party: Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT04232241    
Other Study ID Numbers: HaploMUDStudy
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid, Acute
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases