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

Zhengzhou University

Status and phase: Enrolling; Phase 2

Conditions: Acute Lymphoblastic Leukemia, Adult

Treatments: Drug: Cyclophosphamide; Radiation: TBI; Radiation: TMLI

Study type: Interventional

Funder types: Other

Identifiers

NCT06564545

2024-KY-0210

Details and patient eligibility

About

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.

Enrollment: 276 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Informed Consent: Participants must voluntarily sign a written informed consent form.

2. Age and Gender: Participants should be male or female, aged 18-65 years, inclusive.

3. 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.

4. Remission Status: The participant's leukemia must be in hematologic remission (complete remission, CR) prior to transplantation.

5. Donor Availability: There must be a suitable haploidentical donor available, and the participant must consent to undergo haploidentical hematopoietic stem cell transplantation (haplo-HSCT).

6. 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.

7. 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:

1. The patient has not achieved hematologic remission before transplantation.
2. The patient has chosen a non-haploidentical related donor.
3. The patient has severe cardiac, hepatic, renal, or pulmonary diseases that make them unable to tolerate the conditioning regimen.
4. The patient has an active or refractory infection, or other life-threatening complications.
5. The patient has a history of other malignant tumors, psychiatric disorders, or HIV infection.
6. 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.
7. The investigator deems the patient unsuitable for participation in the study for any other reason.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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276 participants in 2 patient groups

TMLI conditioning group

Experimental group

Description:

Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide

Treatment:

Radiation: TMLI

Drug: Cyclophosphamide

TBI conditioning group

Active Comparator group

Description:

Total Body Irradiation (TBI) plus Cyclophosphamide

Treatment:

Radiation: TBI

Drug: Cyclophosphamide