Haplo-HSCT for Myelofibrosis (HHM)

May 11, 2025 updated by: Sun Yuqian, Peking University People's Hospital

Haploidentical Hematopoietic Stem Cell Transplantation for the Treatment of Myelofibrosis: A Prospective, Single-center Study

Myelofibrosis (MF) is a myeloproliferative neoplasm causing bone marrow failure and high risk of leukemia transformation. JAK2 inhibitors improve symptoms but do not cure MF. Allogeneic stem cell transplantation (allo-HSCT) is the only potential cure, though limited donor availability restricts access. Haploidentical transplantation shows promise but associated with higher graft failure and treatment related mortality. We recently developed a novel regimen of haplo-SCT for MF. This study aims to investigate this novel protocol in a prospective trial to improve MF outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, reactive hyperplasia of bone marrow stromal cells, and secondary inflammation and fibrosis, leading to progressive bone marrow failure and a high risk of acute myeloid leukemia transformation, with a median survival of about 6 years. While JAK2 inhibitors like ruxolitinib have been approved to improve symptoms and survival in MF patients, they do not provide a cure. Allogeneic stem cell transplantation (allo-HSCT) remains the only potential cure, but limited availability of matched sibling and unrelated donors often prevents patients from receiving this treatment. Haploidentical stem cell transplantation has shown good efficacy in leukemia but is less studied in MF, possibly due to concerns about graft failure, complications, and high transplant-related mortality. Our team has applied a novel haploidentical transplantation protocol for treating MF, which has shown promising results in preliminary observations. This study aims to further validate the effectiveness of this protocol through a prospective clinical trial, potentially establishing an effective approach for HSCT in MF and improving overall transplant outcomes.

Study Type

Interventional

Enrollment (Estimated)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Peking University People's Hospital
        • Contact:
          • Yuqian Sun, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

Patients with myelofibrosis who are intended for haploidentical hematopoietic stem cell transplantation, admitted to the Department of Hematology, Peking University People's Hospital.

Description

Inclusion Criteria:

  • Primary disease type: Myelofibrosis (including primary myelofibrosis and myelofibrosis secondary to polycythemia vera or essential thrombocythemia).
  • No matched sibling donor or unrelated donor, with the availability of a haploidentical donor.
  • Signed informed consent.

Exclusion Criteria:

  1. Active infection
  2. Very poor performance status (ECOG score > 2)
  3. Estimated survival time < 30 days
  4. Patient or family unable to cooperate
  5. Considered unsuitable after discussion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Haplo-SCT group
Patients in this group will undergo haploidentical hematopoietic stem cell transplantation for the treatment of myelofibrosis.
Procedure: Haploidentical hematopoietic stem cell transplantation

This is a single-arm study in which all patients will undergo haploidentical hematopoietic stem cell transplantation for the treatment of myelofibrosis.

Pre-transplant Evaluation:

Evaluation includes status of primary Disease, donor specific antibodies (DSA), organ function (assessments for heart, liver, lungs, kidneys, and the nervous system), and Spleen size.

Transplantation Protocol:

Conditioning Regimen:

Dac/TT/Bu/Flu/ATG regimen:

Decitabine 100 mg/m², on day -12. Thiotepa (TT) 5 mg/kg/day, on days -11 and -10. Busulfan 0.8 mg/kg body weight, every 6 hours, on days -8 to -6. Fludarabine 30 mg/m², once daily, on days -6 to -2. Anti-thymocyte globulin (ATG) 2.5 mg/kg body weight, once daily, on days -5 to -2.

Transplant Donor: Haploidentical donor. GVHD (Graft-versus-Host Disease) Prophylaxis Regimen: Cyclosporine, mycophenolate mofetil, and short-course methotrexate for GVHD prevention.

Graft:

Target MNC (Mononuclear Cells): 6-8 × 10⁸/kg. Target CD34+ stem cells: 5 × 10⁶/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative incidence of Good graft function at day 60
Time Frame: Assessment at 60 days post-transplantation
The cumulative incidence of achieving both neutrophil engraftment and platelet engraftment at day 60 after Hematopoietic stem cell transplantation, independent of transfusion and granulocyte growth factor support, using competing risk model.
Assessment at 60 days post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplant-related mortality
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
TRM is defined as death due to any transplantation-related cause other than disease relapse. Transplant-related mortality will be calculated using a competing risks model.
From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
overall survival
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
The time from hematopoietic stem cell transplantation to death from any cause in patients with myelofibrosis. Overall survival will be calculated using the Kaplan-Meier method.
From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
Cumulative Incidence of Relapse
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.

Relapse was defined as disease recurrence. The criteria for relapse include:

  1. Increase in age-adjusted cellularity and abnormal M: E ratio.
  2. Megakaryocytic abnormalities typical of MF (pleomorphism, hyperchromatic, cloud-like nuclei and megakaryocytic clusters).
  3. Increase in grade of reticulin/collagen fibrosis (it should be borne in mind that the previously formed new bone usually takes a long time to be resorbed/resolved and that this should not therefore be used in grading post-transplant unless its density is significantly greater than the pre-transplant biopsy or there is active evidence of continuing new bone deposition).
From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
Incidence of GVHD
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
The incidence refers to the rate at which new cases of GVHD occur within a timeframe. Acute GVHD was classified as symptom presentation before 100 days after alloHCT and chronic GVHD was classified as symptom presentation >100 days after alloHCT. Each organ (skin, liver, and gut) was staged 1 through 4 for Acute (a) GVHD according to modified criteria based on the schema of the Mount Sinai Acute GVHD International Consortium (MAGIC), and patients were also assigned a grade of acute GVHD (I through IV) based on overall severity. Chronic (c) GVHD was graded in accordance with the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease Consensus Criteria.
From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
Disease-free survival
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
The time from hematopoietic stem cell transplantation to the first occurrence of disease relapse, progression, or death from any cause in patients with myelofibrosis.
From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
Neutrophil Engraftment
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
The time to neutrophil engraftment was defined as the first of three consecutive days with an ANC > 0.5 × 109/L.
From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
Platelet Engraftment
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
The time to platelet engraftment was defined as the first of seven consecutive days with a platelet count >20 × 109/L without transfusion support.
From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
Graft failure
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 28 days post-treatment.
Primary GF is defined by an ANC<0.5×109/l by day +28 following stem cell infusion, Hb <80 g/L and platelets <20×109 /L.Secondary GF is currently defined by EBMT criteria as the presence of an ANC<0.5×109/L occurring after initial engraftment and not related to relapse, infection or drug toxicity.
From baseline assessment at enrollment to the follow-up assessment at 28 days post-treatment.
Toxicity of conditioning
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 30 days post-treatment.

Toxicity of conditioning within 30 days of Hematopoietic Stem Cell Transplantation (HSCT) can be graded according to Common Terminology Criteria for Adverse Events (CTCAE):

  1. Grade 1: Mild toxicity that does not require medical intervention.
  2. Grade 2: Moderate toxicity that may require medical intervention.
  3. Grade 3: Severe toxicity that requires significant medical intervention, hospitalization, or results in lasting effects.
  4. Grade 4: Life-threatening toxicity, potentially requiring intensive care.
  5. Grade 5: Death caused by the toxicity reaction.
From baseline assessment at enrollment to the follow-up assessment at 30 days post-treatment.
Grade of Bone Fibrosis
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.
The degree of bone marrow fibrosis as assessed by histopathological examination, categorized according to The European Consensus on grading of bone marrow fibrosis in patients with myelofibrosis after hematopoietic stem cell transplantation.
From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.
Spleen Response
Time Frame: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.

The change in spleen size, typically measured by imaging (e.g., ultrasound, CT scan), after hematopoietic stem cell transplantation, categorized as complete response, partial response, or no response according to the response criteria of IWG-MRT and ELN:

  • Complete Response (CR): The spleen is no longer palpable or measurable by imaging after treatment, indicating a full resolution of splenomegaly.
  • Partial Response (PR): A significant reduction in spleen size, typically defined as a reduction of at least 35% in spleen volume or a decrease in palpable spleen size.
  • No Response (NR): No reduction in spleen size, or the spleen size remains stable or worsens.
  • Progressive Disease (PD): The spleen increases in size after treatment, indicating worsening of splenomegaly.
From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2024

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

November 3, 2024

First Submitted That Met QC Criteria

November 3, 2024

First Posted (Actual)

November 5, 2024

Study Record Updates

Last Update Posted (Actual)

May 14, 2025

Last Update Submitted That Met QC Criteria

May 11, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024PHB400-001
  • Peking University (Peking University)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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