Clinical trial NCT06674382: Haplo-HSCT for Myelofibrosis
Official title: Haploidentical Hematopoietic Stem Cell Transplantation for the Treatment of Myelofibrosis: A Prospective, Single-center Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Myelofibrosis
Keywords: Haplo-HSCT
myelofibrosis
MF
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2024-11-05
Enrollment: 39
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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:

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

Primary outcomes:
measure: Cumulative incidence of Good graft function at day 60
timeFrame: Assessment at 60 days post-transplantation
Secondary outcomes:
measure: Transplant-related mortality
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
measure: overall survival
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
measure: Cumulative Incidence of Relapse
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
measure: Incidence of GVHD
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
measure: Disease-free survival
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.
measure: Neutrophil Engraftment
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
measure: Platelet Engraftment
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.
measure: Graft failure
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 28 days post-treatment.
measure: Toxicity of conditioning
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 30 days post-treatment.
measure: Grade of Bone Fibrosis
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.
measure: Spleen Response
timeFrame: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
Study officials:
References:
citation: 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 myelofibrosis who are candidates for allogeneic hematopoietic cell transplantation: a Position Paper on behalf of the Chronic Malignancies Working Party of the EBMT. Lancet Haematol. 2023 Jan;10(1):e59-e70. doi: 10.1016/S2352-3026(22)00330-1. Epub 2022 Dec 6.
citation: 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.
citation: 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.