Haplo-HSCT for Myelofibrosis

Official title

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

Overview

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.

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.

Interventions

• 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

Primary outcome measures

• Cumulative incidence of Good graft function at day 60 [Time frame: Assessment at 60 days post-transplantation]

Secondary outcome measures (11)

• Transplant-related mortality [Time frame: 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.]
• Cumulative Incidence of Relapse [Time frame: 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.]
• Disease-free survival [Time frame: 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.]
• Platelet Engraftment [Time frame: 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.]
• Toxicity of conditioning [Time frame: 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.]
• Spleen Response [Time frame: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Publications

• Polverelli N, Hernandez-Boluda JC, Czerw T, Barbui T, D'Adda M, Deeg HJ, Ditschkowski M, Harrison C, Kroger NM, Mesa R, Passamonti F, Palandri F, Pemmaraju N, Popat U, Rondelli D, Vannucchi AM, Verstovsek S, Robin M, Colecchia A, Grazioli L, Damiani E, Russo D, Brady J, Patch D, Blamek S, Damaj GL, Hayden P, McLornan DP, Yakoub-Agha I. Splenomegaly in patients with primary or secondary myelofibros PMID 36493799
• Cervantes F, Dupriez B, Passamonti F, Vannucchi AM, Morra E, Reilly JT, Demory JL, Rumi E, Guglielmelli P, Roncoroni E, Tefferi A, Pereira A. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012 Aug 20;30(24):2981-7. doi: 10.1200/JCO.2012.42.0240. Epub 2012 Jul 23. PMID 22826273
• Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020 Oct;191(2):152-170. doi: 10.1111/bjh.16576. Epub 2020 Mar 20. PMID 32196650

Identifiers

NCT: NCT06674382 · 2024PHB400-001 · Peking University

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗