AzTrials
AzTrials

Acute Myeloid LeukemiaPhase 3MacHaploMudNCT03655145

HLA 10/10 Matched Unrelated Donor vs Haploidentical Allogenic Hematopoietic Stem Cell Transplantation

A Phase 3 study testing Haplo donor stem cell transplantation and HLA 10/10 MUD stem cell transplantation in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Assistance Publique - Hôpitaux de Paris.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The MAC-HAPLO-MUD trial is a randomized prospective phase III trial comparing HLA 10/10 matched unrelated donor and haploidentical allogeneic hematopoietic stem cell transplantation after myeloablative conditioning regimen in patients, age 15 years or older, with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic… Read more about this study

Who is it for?
Ages 15 to 55 years
What is being tested?
Haplo donor stem cell transplantation and HLA 10/10 MUD stem cell transplantation
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
344 participants
Where
No sites listed yet
Study dates
Aug 2018to Jun 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 to 55 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • With AML/ALL/SMD/SMP requiring allogeneic stem cell transplantation
  • In complete response (CR) for AML/ALL or in CR, or partial response (PR) or non pre-treated for SMD/SMP *
  • Without a HLA matched related donor available
  • With a good probability to have a HLA-10/10 matched donor available (the patient needs to have at least 5 MUD identified within the book "BMDW (Bone Marrow Donors Worldwide)"
  • With identification of a haploidentical donor (brother, sister, parents, adult children or cousin)
  • Absence of donor specific antibody (DSA) detected in the patient with a MFI ≥ 2000 (antibodies directed towards the distinct haplotype between donor and recipient)
Show all 15Show fewer
  • With usual criteria for hematopoietic stem cell transplant (HSCT):
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • No severe and uncontrolled infection
  • Cardiac function compatible with high dose of cyclophosphamide
  • Adequate organ function: aspartate transaminase (ASAT) and alanine aminotransferase (ALAT) ≤ 2N, total bilirubin ≤ 1.5N, creatinine clearance ≥30ml/min (except if those abnormalities are linked to the hematological disease)
  • With health insurance coverage
  • Understand informed consent or optimal treatment and follow-up
  • Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment and within 12 months for women and 6 months for men after the last dose of cyclophosphamide
  • Having signed a written informed consent (2 parents for patients aged less than 18)

Who cannot join

  • Presence of donor specific antibody (DSA) with a MFI ≥ 2000 detected in the patient
  • History of Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
  • Uncontrolled infection
  • Seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive polymerase chain reaction (PCR) hepatitis B virus (HBV) or hepatitis C virus (HCV) and hepatic cytolysis due to HBV
  • Yellow fever vaccine within 2 months before transplantation
  • Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction <50%
Show all 15Show fewer
  • Heart failure according to New York Heart Association (NYHA) (II or more)
  • Urinary tract obstruction
  • Contraindications to treatments used during the research
  • Preexisting acute hemorrhagic cystitis
  • Renal failure with creatinine clearance <30ml / min
  • Pregnancy ( β- human chorionic gonadotropin (β-HCG positive)) or breast-feeding
  • Any debilitating medical or psychiatric illness which would preclude the realization of the SCT or the understanding of the protocol
  • Under protection by law (tutorship or curatorship)
  • Unwilling or unable to comply with the protocol

Trial locations and contacts

No sites are listed yet.

Régis Peffault de Latour contact

+33142385073

regis.peffaultdelatour@aphp.fr

Sylvie Chevret contact

+33142499742

sylvie.chevret@paris7.jussieu.fr

About this study

Official title: Randomized Prospective Phase III Clinical Trial Comparing HLA 10/10 Matched Unrelated Donor and Haploidentical Allogenic Hematopoietic Stem Cell Transplantation After Myeloablative Conditioning Regimen

The MAC-HAPLO-MUD trial is a randomized prospective phase III trial comparing HLA 10/10 matched unrelated donor and haploidentical allogeneic hematopoietic stem cell transplantation after myeloablative conditioning regimen in patients, age 15 years or older, with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) or Myeloproliferative Syndrome (SMP) or Myelodysplastic Syndromes (SMD) and requiring allogeneic hematopoietic stem cell transplantation. Primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

Read the detailed description

An unrelated adult donor who is HLA-matched to the recipient at the allele-level (at HLA-A, -B, -C, -DQB1 and -DRB1) is considered the best choice in the absence of an HLA-matched sibling for patients needing hematopoietic stem cell transplantation (SCT).

However, using matched unrelated donors (MUD) is limited by (1) a prolonged time to identify and schedule donation for some MUD allowing some patients to relapse before transplantation can be performed, and (2) limited availability of fully HLA-MUD for the non-Caucasian population.

Alternative donors are used for transplantation in patients without a fully-MUD including single HLA mismatched unrelated donor, unrelated umbilical cord blood and grafts from haploidentical related donors but are associated with higher non-relapse mortality and delayed immune reconstitution.

A more recent strategy for haploidentical (haplo) related donor SCT (haplo-SCT) has improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy).

From retrospective studies, haplo-SCT with PTCy are associated with similar overall and progression-free survivals as with MUD stem cell transplantation (MUD-SCT), but with lower rates of toxicity and graft versus host disease (GvHD), and thus potentially better results than MUD-SCT after reduced intensity conditioning (RIC) regimen. Haplo-SCT with PTCy is thus highly discussed nowadays motivating prospective trials to confirm the benefit of this procedure.

In the setting of a myeloablative conditioning (MAC) regimen in adults with high risk hematological malignancies, few retrospective non-controlled registry studies recently suggest that outcomes after haplo-SCT using PTCy approach might also be superior in terms of GVHD free survival to that after MUD stem cell transplantation (MUD-SCT).

The investigators propose to address this question, in a randomized prospective phase III clinical trial comparing HLA 10/10 MUD and haplo-SCT after MAC regimen. The stem cell source will be bone marrow for haploidentical SCT and peripheral blood stem cell (PBSC) for HLA-matched unrelated transplantation.

The primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

Being tested
Haplo donor stem cell transplantation, HLA 10/10 MUD stem cell transplantation
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Haplo donor stem cell transplantationOther

    The algorithm for selection of haploidentical donor has been defined by the french society for stem cell transplantation The stem cell source will be bone marrow for haploidentical transplantation.The bone marrow collection is carried out according to the practice of each centre with a minimal target dose of 3x108 TNC/kg.

  • HLA 10/10 MUD stem cell transplantationOther

    HLA 10/10 matched unrelated donor myeloablative transplantation

Study groups in NCT03655145
Study groupRoleWhat they receive
Haploidentical donor stem cell transplantationExperimentalThe stem cell source will be bone marrow for haploidentical transplantation.The bone marrow collection is carried out according to the practice of each centre with a minimal target dose of 3x108 TNC/kg.
Receives: Other: Haplo donor stem cell transplantation
HLA 10/10 MUD stem cell transplantationActive comparatorThe stem cell source will be peripheral blood stem cell for HLA-matched unrelated transplantation.Peripheral blood stem cell (PBSC) for HLA-matched unrelated SCT will be mobilized by G-CSF (Neupogen®) administered to the donor from Day-4 to Day-1 subcutaneously (10µg/kg/day) with the minimal target dose of 4.106 CD34+ cells/kg.
Receives: Other: HLA 10/10 MUD stem cell transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

    One year progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

    -Relapse evaluation:

    For myeloid malignancies, the relapse will be defined by the reappearance of leukemic cells after SCT.

    For ALL, the relapse will be defined by: the reappearance of leukemic cells after SCT and/or an increase of at least 50 % of the smallest measure of any lymphnode considered abnormal in the pre-transplantation period for patients in partial response and in non-responders and/or the appearance of any new lesion in comparison with the pre-transplantation period evaluation.

    • GvHD evaluation:

    Grading of acute GVHD will be performed according to the classification of Glusckberg.

    Grading of chronic GVHD will be performed according to the NIH classification.

    Measured: 12 months

Secondary outcomes (49)

  1. Time interval between indication of stem cell transplantation (SCT) and transplant

    Measured: 24 months

  2. Engraftment

    Engraftment: at least 3 consecutive days with neutrophils > 0.5 G/L, with platelets > 20 G/L

    Measured: at 24 months

  3. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 1 month

  4. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 1 month

  5. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 2 months

  6. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 2 months

  7. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 3 months

  8. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 3 months

  9. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 6 months

  10. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 6 months

  11. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 12 months

  12. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 12 months

  13. Numbers of neutrophils

    Absolute numbers of neutrophils

    Measured: at 24 months

  14. Numbers of platelets

    Absolute numbers of platelets

    Measured: at 24 months

  15. Use of growth factors

    Use of growth factors for poor hematopoietic reconstitution

    Measured: at 12 months

  16. Immune reconstitution

    Immune reconstitution by analyzing T, B, Natural Killer (NK), regulatory T cell levels in the peripheral blood

    Measured: at 1 month post transplantation

  17. Immune reconstitution

    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Measured: at 3 months post transplantation

  18. Immune reconstitution

    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Measured: at 6 months post transplantation

  19. Immune reconstitution

    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Measured: at 12 months post transplantation

  20. Immune reconstitution

    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood

    Measured: at 24 months post transplantation

  21. Iron overload estimation

    Measured: at 1 month

  22. Iron overload estimation

    Measured: at 3 months

  23. Iron overload estimation

    Measured: at 6 months

  24. Iron overload estimation

    Measured: at 12 months

  25. Iron overload estimation

    Measured: at 24 months

  26. Chimerism

    Measured: at 1 month

  27. Chimerism

    Measured: at 3 months

  28. Chimerism

    Measured: at 6 months

  29. Chimerism

    Measured: at 12 months

  30. Acute GvHD

    Incidence of acute GvHD

    Measured: at 24 months

  31. First line treatment

    Measured: 24 months

  32. Response to steroids

    Measured: 24 months

  33. Treatment courses for refractory aGVHD

    Measured: 24 months

  34. Relapse

    Incidence of relapse

    Measured: 24 months

  35. Progression free survival

    Measured: 24 months

  36. Severe infections (CTAE grade 3-4)

    Measured: 12 months

  37. Cytomegalovirus (CMV)

    Incidence of CMV

    Measured: 12 months

  38. Epstein-Barr virus (EBV)

    Incidence of EBV reactivation

    Measured: 12 months

  39. Veno-occlusive disease (VOD)

    Incidence of veno-occlusive disease

    Measured: 3 months

  40. Severity of veno-occlusive disease (VOD)

    Severity of veno-occlusive disease. VOD severity will be assessed using new EBMT criteria (Mohty et al., 2016). EBMT criteria for grading VOD severity in adult patients are based on the level of bilirubin and its rate of change, liver function (transaminase), weight increase, renal function and the kinetic of their onset (Mohty et al., 2016). This grading system is divided into five categories as following: mild, moderate; severe, very severe; and death.

    Mohty M., Malard F., Abecassis M., Aerts E., Alaskar AS. et al. (2016). Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplantation 51,906-912.

    Measured: 3 months

  41. Cardiac toxicities

    Incidence of cardiac toxicities

    Measured: 12 months

  42. Non-relapse mortality

    Measured: 12 months

  43. Overall survival

    Time between death and inclusion

    Measured: 24 months

  44. Quality of life post transplantation: EORTC QLQ-C30- v3

    Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.

    EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.

    Measured: 1 week post-transplantation

  45. Quality of life at 3 months: EORTC QLQ-C30- v3

    Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.

    EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.

    Measured: 3 months

  46. Quality of life at 6 months: EORTC QLQ-C30- v3

    Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.

    EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.

    Measured: 6 months

  47. Quality of life at 12 months: EORTC QLQ-C30- v3

    Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.

    EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.

    Measured: 12 months

  48. Quality of life at 24 months: EORTC QLQ-C30- v3

    Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.

    EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.

    Measured: 24 months

  49. Number of new days of hospitalization after the hospitalization for transplantation

    Measured: at 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study startAug 2018 (estimated)
  3. Primary completionJun 2019 (estimated)
  4. Study completionJun 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized prospective Phase III clinical trial comparing HLA 10/10 matched unrelated donor (standard arm) and haploidentical allogeneic hematopoietic stem cell transplantation (experimental arm) after myeloablative conditioning regimen
Masking
None (open label)
Enrolment
344 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03655145
Sponsor's protocol ID
AOM 17030
Acronym
MacHaploMud
Status last verified
May 2018
First submitted
6 Jun 2018
Last updated
31 Aug 2018
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Haplo donor stem cell transplantation and HLA 10/10 MUD stem cell transplantation in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Assistance Publique - Hôpitaux de Paris.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Régis Peffault de Latour (+33142385073, regis.peffaultdelatour@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD. (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03655145.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in