Unrelated Umbilical Cord Blood Stem Cell Combined With Azacitidine Based Treatment for Advanced MDS,CMML-2 and sAML

Myelodysplastic Syndromes Clinical Trial

Official title: A Perspective, Multicenter, Open-label and Observational Trial for Unrelated Umbilical Cord Blood Stem Cell Microtransplantation Combined With Azacitidine Based Treatment for Advanced MDS,CMML-2 and Secondary AML.

Status Recruiting

Clinical Trial Summary

This research is being done to study the efficacy and safety of unrelated umbilical cord blood stem cell microtransplantation combined with azacitidine(AZA) based treatment for advanced myelodysplastic syndromes(MDS), Chronic myelomonocytic leukemia-2(CMML-2) and secondary acute myeloid leukemia(sAML). The study protocol involved unrelated umbilical cord blood stem cell combined with azacitidine based treatment, which including azacitidine alone and azacitidine plus a targeted agent or chemotherapy agent.

Clinical Trial Description

This is a perspective, multicenter, open-label and observational trial for unrelated umbilical cord blood stem cell microtransplantation combined with azacitidine based treatment for advanced MDS,CMML-2 and secondary AML. The study protocol is AZA /AZA+ combined with umbilical cord blood stem cell microtransplantation for patients who met the inclusion criteria in higher-risk MDS(HR-MDS), CMML and sAML.

Demethylating agents are mainly decitabine (DAC) and azacitidine (AZA), both of which have been approved by the FDA for the treatment of MDS. The FDA has also approved hypomethylating agents for the treatment of CMML.Secondary acute myeloid leukemia (sAML) refers to acute myeloid leukemia with progression from a preexisting hematologic disease, such as myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPN) (excluding chronic myelomonocytic leukemia). Currently, there is no standard treatment for sAML. Based on the results of retrospective studies and clinical trials, the efficacy of hypomethylating agents in the treatment of sAML is not weaker than that of traditional intensive induction therapy and other reduced-intensity therapy or best supportive care.

The development of microtransplantation has provided new treatment modalities in patients who are not candidates for conventional allogeneic hematopoietic stem cell transplantation. In China, Huisheng Ai team proposed the concept of micro-transplantation. Micro-transplantation (MST) is a new concept and method that combines conventional chemotherapy or targeted drugs with allogeneic stem cell infusion. Microtransplantation is combined with infusion of G-CSF mobilized peripheral blood stem cells (G-PBSC) from HLA-mismatched donors on the basis of killing leukemia cells by chemotherapy or targeted drugs. Thus, donor microchimerism (donor cells <1-5%) can be formed to induce donor/recipient anti-leukemia (GVL/RVL) effect and promote hematopoietic recovery in recipients without full donor engraftment and almost no risk of GVHD. The clinical results have also been verified in several research centers in the United States, Australia, Spain and other countries, which show that micro-transplantation technology can promote hematopoietic recovery, produce graft-versus-tumor effect and recipientversus-tumor effect, and provide a new safe and effective treatment method for the treatment of hematological diseases and solid tumors.

Participants will receive unrelated umbilical cord blood transfusion during at least 1-2 cycles of treatment.The specific process is as follows:

A single unit of unrelated umbilical cord blood was reinfused within 24-72 hours after the end of AZA or chemotherapy, and the longest delay was 96 hours after the end of chemotherapy. The umbilical cord blood was matched at 0-3/10 locus.

Specific treatment options:

1. AZA monotherapy:

Azacitidine 75mg·m-2·d-1, d1-d7, subcutaneous injection;

2. VA :

Azacitidine 75mg·m-2·d-1, d1-d7, subcutaneous injection; Venetoclax (VEN) 100mg d1,200mg d2,400mg d3 to d14, orally.

3. VAH :

Azacitidine 75mg·m-2·d-1, d1-d7, subcutaneous injection; Venetoclax (VEN) 100mg d1, 200mg d2,400mg d3 to d14, orally. Homoharringtonine injection (HHT) 2-3mg d1 to d14 was intravenously injected. During the period, the medication time was adjusted according to the patient's blood condition and complications If severe adverse reactions (such as grade 3 or above infection and bone marrow suppression) occurred, the next course of treatment was postponed according to the situation.

Microtransplantation of umbilical cord blood: single unit of unrelated cord blood (HLA 0-5/10 or 0-3/6 matched, TNC 1-2×107/Kg body weight), AZA or homoharringtonine infusion 24-72 hours after the end of injection.

It is expected that about 50 patients will take part in this research study. ;

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia-2
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Neoplasm Metastasis
• Preleukemia
• Secondary Acute Myeloid Leukemia

• NCT number: NCT05584761
• Study type: Interventional
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Fei Huang, MD
• Phone: +8615950523133
• Email: huangfei0815@126.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2022
• Completion date: December 31, 2026