A Prospective, Open-label, Randomized Controlled, Multicenter Clinical Study of Haplo-HSCT Using a TBI or TMLI Conditioning Regimen for Adult ALL

Official title

A Prospective, Open-label, Randomized Controlled, Multicenter Clinical Study of Haploidentical Hematopoietic Stem Cell Transplantation Using a TBI or TMLI Conditioning Regimen for Adult Acute Lymphoblastic Leukemia

Overview

This study aims to compare the effects of two different conditioning regimens on patients with acute lymphoblastic leukemia (ALL) undergoing haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT): Total Body Irradiation (TBI) and Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI). Both regimens are supported and recommended by literature; however, there is no definitive evidence favoring one over the other. We hypothesize that the TMLI regimen, compared to the TBI regimen, may more effectively eliminate leukemia cells in the bone marrow and lymphoid tissues, thereby reducing the risk of relapse, while also minimizing damage to normal tissues, thus reducing conditioning-related toxicity and transplant-related mortality. This study aims to provide evidence for the optimal conditioning regimen for haplo-HSCT in adult ALL patients, with the goal of improving patient quality of life and survival outcomes.

Interventions

• Radiation TBI
  The total dose of TBI is 12 Gy, administered on days -7, -6, and -5, with 2 Gy per fraction, twice daily, for a total of 6 fractions.
• Radiation TMLI
  The total dose of TMLI is 12 Gy, administered on days -7, -6, and -5, with 2 Gy per fraction, twice daily, for a total of 6 fractions.
• Drug Cyclophosphamide
  The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.

Primary outcome measures

• Relapse-free survival (RFS) [Time frame: 2 years]
• acute Graft Versus Host Disease (aGVHD) [Time frame: 100 days]
• Overall Survival (OS) [Time frame: 2 years]

Secondary outcome measures (3)

• Transplantation Related Mortality (TRM) [Time frame: 100 days]
• Relapse Rate (RR) [Time frame: 2 years]
• Conditioning-related Adverse Events (CRAE) [Time frame: 30 days]

Eligibility criteria

Inclusion criteria

• Informed Consent: Participants must voluntarily sign a written informed consent form.
• Age and Gender: Participants should be male or female, aged 18-65 years, inclusive.
• Diagnosis: Participants must be diagnosed with acute lymphoblastic leukemia (ALL) according to World Health Organization (WHO) criteria, and the diagnosis must apply to adults aged 18-65 years.
• Remission Status: The participant's leukemia must be in hematologic remission (complete remission, CR) prior to transplantation.
• Donor Availability: There must be a suitable haploidentical donor available, and the participant must consent to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).
• Karnofsky Performance Status: The participant must have a Karnofsky score of 70 or higher, indicating that they are capable of caring for themselves and carrying out normal activities. Additionally, they must not have significant organ dysfunction, defined by the following:

• Cardiac Function: New York Heart Association (NYHA) classification of class II or lower.
• Liver Function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be no more than 2.5 times the upper limit of normal. Bilirubin levels should be no more than 2 times the upper limit of normal.
• Renal Function: Serum creatinine levels should be no more than 1.5 times the upper limit of normal, or the creatinine clearance rate should be at least 60 ml/min.
• Pulmonary Function: Participants should not experience significant dyspnea, should not require oxygen therapy, should not have interstitial lung disease, and should not have any active pulmonary infections.
• Reproductive Health:

• Women of childbearing potential must test negative for pregnancy with a Human Chorionic Gonadotropin (HCG) test, confirmed by immunofluorescence during both screening and baseline periods. They must also agree to use effective contraception for at least one year following the transplantation.
• Male participants with female partners of childbearing potential must agree to use effective barrier contraception and refrain from sperm donation for at least one year following the transplantation.

Exclusion criteria

To be eligible for inclusion in the study, participants must not meet any of the following criteria:

• The patient has not achieved hematologic remission before transplantation.
• The patient has chosen a non-haploidentical related donor.
• The patient has severe cardiac, hepatic, renal, or pulmonary diseases that make them unable to tolerate the conditioning regimen.
• The patient has an active or refractory infection, or other life-threatening complications.
• The patient has a history of other malignant tumors, psychiatric disorders, or HIV infection.
• The patient refuses to sign the informed consent form, is unwilling to comply with clinical follow-up required by the study, or does not consent to the use of their data to support future research, project presentations, and clinical practices.
• The investigator deems the patient unsuitable for participation in the study for any other reason.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Zhengzhou University — Zhengzhou

Identifiers

NCT: NCT06564545 · 2024-KY-0210

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗