Clinical trial NCT05902416: Clinical Registration Study of Haplo-HSCT for Elderly Patients With Acute Leukemia/ Myelodysplastic Syndrome
Official title: Clinical Registration Study of Haploidentical Stem Cell Transplantation for Elderly Patients With Acute Leukemia or Myelodysplastic Syndrome
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Leukemia
Myelodysplastic Syndromes
Keywords: RIC regimen
Elderly
comorbidity
transplant-related mortality
Haplo-HSCT
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 120
Sex: ALL
Minimum age (years): 55
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients ≥55 years of age and \<70 years of age, with acute leukemia or MDS (with or without HCT-CI≥3)

Brief summary: This study is an open, prospective, single-center, single-arm study expanded based on the study of NCT03412409.The primary objective of this study is to evaluate the transplantation efficacy of the RIC conditioning regimen in elderly patients receiving the transplantation of haploidentical hematopoietic stem cells. Elderly patients are defined as ≥55 years of age; High comorbidity is defined as an HCT-CI score ≥3.Primary endpoint is 1-year LFS. Secondary endpoints are 1-year OS and 1-year TRM, Other indicators to be assessed in this study include acute GVHD, chronic GVHD, CMV activation, EBV activation, engraftment.

Detailed description: Currently, the transplantation of allogeneic hematopoietic stem cells (allo-SCT) remains the main and often the only cure for neoplastic hematologic disorder or hematological malignancy. Although HLA-matched siblings are the preferred donor, not all patients have one; or it needs to wait so long to obtain it that the optimal time for transplantation is past. Haploidentical transplants as secondary donors are more readily available and may be considered in combination with the conditions of the donor and the patient and the experience of the transplant facility when a matched donor is unavailable. Currently, haploidentical transplantation has been commonly applied to young patients. On the other hand, TRM rate will be higher in elderly patients and patients with high comorbidity due to tolerability, thus reducing the ultimate benefits of patients.

The choice of conditioning regimen is influenced by multiple factors such as disease type, disease status, physical condition, and source of transplant donor. For patients over 55 years of age or with a comorbidity index ≥3, the RIC regimen may be considered to improve patient tolerability. RIC regimen can improve the tolerability of patients receive transplants, while regimens such as immune suppressants are also needed to control and improve the overall transplant efficiency. An in-depth study of RIC regimen will help improve the effects of transplantation and increase patient benefits.

This study is aim to evaluate the efficacy of RIC conditioning regimen for transplantation in elderly patients or patients with high comorbidity receiving the transplantation of haploidentical hematopoietic stem cells.

Drugs and dosage of conditioning regimen:

Ara-C(2g/m2/day,-10 days to -9 days),Bu(9.6mg/kg,-8 days to -6 days),Flu(30mg/m2/day,-6 days to -2 days),Cy(1,000mg/m2/day,-5 days to -4 days),semustine(250mg/m2,-3 days),ATG(10 mg/kg,-5 to -2 days).

Supportive care:

CsA: To prevent GVHD, CsA therapy starts 9 days before transplantation at 2.5 mg/kg intravenously until gut function returns to normal after transplantation; CsA is then orally administered. MMF: To prevent GVHD, 0.5g of MMF is orally administered every 12 hours 9 days before transplantation until hematopoietic function is restored after transplantation. MTX: To prevent GVHD, MTX is intravenously administered at 15 mg/m2 on day 1 after transplantation. On days 3, 6 and 11 after transplantation, MTX is intravenously administered at 10 mg/m2. Ganciclovir: To prevent post-transplantation CMV infection, it is administered 2 days before transplantation, and to prevent post-transplantation CMV infection, it is orally administered at 400 mg twice a day until the end of all immunosuppressive medications.

Primary endpoint is 1-year LFS. Secondary endpoints are 1-year OS and 1-year TRM, Other indicators to be assessed in this study include acute GVHD, chronic GVHD, CMV activation, EBV activation, engraftment.

CMV and EBV Tests are performed twice weekly for monitor based on PCR means.

The follow-up period designed for this study is 1 year, with the day of hematopoietic stem cell transplantation as Day 1 and the visit dates of Day 0, 1st month, 2nd month, 3rd month, 6th month and 12th month. The end of the study is defined as the date of the last visit of the last patient (LPLV).

Eligibility criteria: Inclusion Criteria:

* Patients ≥55 years of age and \<70 years of age, with acute leukemia or MDS (with or without HCT-CI≥3);
* Patients eligible for the transplantation of allogeneic hematopoietic stem cells;
* Patients unavailable with HLA matched donors but available with haploidentical donors;
* Voluntary participation in this study and signing the informed consent form.

Exclusion Criteria:

* Patients with the severe infections;
* Pregnant or lactating women or female and male subjects of childbearing age and their spouses who are unable to secure effective contraception during the dosing period and within 90 days after the end of the dosing period.
* Patients who are not eligible for hematopoietic stem cell transplantation;
* Patients who are enrolled in other clinical trials within 1 month;
* Patients who may not be able to complete the study for other reasons, or may be considered by the investigator not suitable to participate in the study;
* Patients unable to properly understand or refusing to accept the informed consent form.

Primary outcomes:
measure: 1-year LFS
timeFrame: Participants will be followed for an expected average of 1 years
Secondary outcomes:
measure: 1-year OS
timeFrame: Participants will be followed for an expected average of 1 years
measure: 1-year TRM
timeFrame: Participants will be followed for an expected average of 1 years
Other outcomes:
measure: Adverse event
timeFrame: Participants will be followed for an expected average of 1 years
measure: Engraftment rate
timeFrame: Participants will be followed for an expected average of 1 years
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
References: