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

February 16, 2025 updated by: Xiangbo Wan, The First Affiliated Hospital of Zhengzhou University

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

This study aims to compare the effects of two different conditioning regimens on patients with acute lymphoblastic leukemia (ALL) undergoing matched sibling donor hematopoietic stem cell transplantation (MSD-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 MSD-HSCT in adult ALL patients, with the goal of improving patient quality of life and survival outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

170

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China, 450001
        • Recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
          • Wan Xiangbo Xiangbo Wan
          • Phone Number: 86-037167963114

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 mathced sibling donor available, and the participant must consent to undergo MSD hematopoietic stem cell transplantation (MSD-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-MSD 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMLI conditioning group
Total Marrow, Central Nervous System and Lymphoid Irradiation (TMLI) plus Cyclophosphamide
Drug: Cyclophosphamide
The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.
Other Names:
  • CTX
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.
Active Comparator: TBI conditioning group
Total Body Irradiation (TBI) plus Cyclophosphamide
Drug: Cyclophosphamide
The total dose of cyclophosphamide is 120 mg/kg, administered over 2 days on days -4 and -3.
Other Names:
  • CTX
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse-free survival (RFS)
Time Frame: 2 years
RFS is defined as the time from transplantation to the first relapse or death, with RFS is defined as the time from transplantation to the first relapse or death, with the date of the last follow-up as the endpoint.
2 years
acute Graft Versus Host Disease (aGVHD)
Time Frame: 100 days
The incidence of aGVHD within 100 days post-transplant.
100 days
Overall Survival (OS)
Time Frame: 2 years
OS is defined as the time from transplantation to death, with the date of the last follow-up as the endpoint.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse Rate (RR)
Time Frame: 2 years
The incidence ratio of leukemia relapse in 2 years.
2 years
Conditioning-related Adverse Events (CRAE)
Time Frame: 30 days
Based on CTCAE v5.0.
30 days
Transplantation Related Mortality (TRM)
Time Frame: 2 years
The incidence of TRM in 2 years.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Zhengzhou University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2025

Primary Completion (Estimated)

August 31, 2029

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

July 4, 2024

First Submitted That Met QC Criteria

August 15, 2024

First Posted (Actual)

August 16, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 16, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-KY-0211

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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