Total Body Irradiation for Acute Leukemia

Overseen By Preston Clairborne, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: DNA methyltransferase inhibitors

Disqualifiers: Prior BMT, Active malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different doses of total body irradiation (a type of radiation therapy) to treat individuals with acute leukemia undergoing their first bone marrow transplant. The researchers aim to determine which dose helps patients remain free from graft-versus-host disease (a complication where donor cells attack the patient's body) and avoid leukemia relapse. Suitable candidates for this trial include those with acute leukemia who have less than 5% cancer cells in their bone marrow and a matching bone marrow donor.

As an unphased trial, this study provides patients the opportunity to contribute to important research that could enhance future leukemia treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that total body irradiation is safe for patients with acute leukemia?

Studies have shown that Total Body Irradiation (TBI) can be a safe treatment option for blood cancers like leukemia. One study found TBI to be safe even for children with blood cancers, regardless of the stem cell transplant source, indicating its safety across different patient groups.

Research comparing TBI to chemotherapy has found that TBI usually results in fewer severe side effects, suggesting that patients often tolerate TBI better than some other treatments. Another study linked TBI to better survival rates and a lower chance of cancer recurrence compared to chemotherapy alone.

Overall, TBI has demonstrated a good safety record and is well-tolerated in similar patient groups. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Total Body Irradiation (TBI) for acute leukemia because it offers a targeted approach that conditions the entire body before stem cell transplantation. Unlike standard treatments that might focus on specific areas, TBI involves delivering radiation uniformly across the body, potentially enhancing the effectiveness of subsequent stem cell infusions. This method may better prepare the body to accept new, healthy stem cells by reducing the likelihood of residual cancer cells. Additionally, the trial explores different radiation doses (200 cGy and 400 cGy), which could help determine the most effective and safest level for patients.

What evidence suggests that total body irradiation might be an effective treatment for acute leukemia?

Research has shown that total body irradiation (TBI) can effectively treat leukemia when administered before a bone marrow transplant. Studies have found that TBI offers survival rates similar to chemotherapy, both overall and without leukemia. In this trial, participants will receive different doses of TBI, specifically 200 cGy or 400 cGy, to evaluate their effectiveness. Evidence suggests that higher doses of TBI might enhance its cancer-fighting ability, improve the engraftment of new bone marrow, and reduce the chance of disease recurrence. Researchers are examining these different doses of TBI to determine if they can improve outcomes, such as survival without graft-versus-host disease. Overall, TBI remains a promising option for patients undergoing treatment for acute leukemia. ^{2 3 6 7 8}

Who Is on the Research Team?

Jonathan Webster

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for patients of any age with acute leukemia (AML, ALL, or mixed/ambiguous lineage) who are undergoing their first allogeneic blood or marrow transplant. Eligible participants include those with a history of myeloproliferative neoplasm (MPN), myelodysplastic syndrome/neoplasm (MDS), and/or MDS/MPN-overlap if they've had specific prior treatments.

Inclusion Criteria

I have been diagnosed with myelodysplastic syndrome.

My leukemia is of a mixed or unclear type, without a specific blast count needed.

I was diagnosed with acute myeloid leukemia without prior conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive reduced-intensity conditioning with chemotherapy and total body irradiation (TBI) before stem cell transplantation

1 week

Daily visits for chemotherapy and TBI administration

Transplantation

Stem cell transplantation is performed after conditioning regimen

1 day

Inpatient stay for transplantation procedure

Post-Transplantation Treatment

Participants receive post-transplantation cyclophosphamide and other medications to prevent graft-versus-host disease

2 weeks

Multiple visits for medication administration

Follow-up

Participants are monitored for safety, engraftment, and effectiveness of the transplant

2 years

Regular follow-up visits, frequency based on institutional protocol

What Are the Treatments Tested in This Trial?

Interventions

• Total Body Irradiation

Trial Overview The study tests two levels of total body irradiation: 200 cGy versus 400 cGy as part of reduced-intensity conditioning before a bone marrow transplant. The goal is to see which dose better prevents graft-versus-host disease while maintaining relapse-free survival in acute leukemia patients.

How Is the Trial Designed?

Group I: TBI: 200 Centigray (cGy) Active Control 1 Intervention

200 cGy TBI is administered based on randomization in a single fraction on Day -3, -2, or -1, depending on if and how many days of rest are permitted. A day of rest occurring after preparative regimen completion and prior to stem cell infusion, is not routinely scheduled. Up to two days of rest may be added in this window based on logistical considerations or clinically as indicated. For one day of rest, TBI would be administered on Day -2. For two days of rest, TBI would be administered on Day -3.

Group II: TBI: 400 cGy Active Control 1 Intervention

400 cGy TBI is administered based on randomization in a single fraction on Day -3, -2, or -1, depending on if and how many days of rest are permitted. A day of rest occurring after preparative regimen completion and prior to stem cell infusion, is not routinely scheduled. Up to two days of rest may be added in this window based on logistical considerations or clinically as indicated. For one day of rest, TBI would be administered on Day -2. For two days of rest, TBI would be administered on Day -3.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Published Research Related to This Trial

In a study of 110 adult patients with acute lymphoblastic leukemia treated with total body irradiation (TBI), the 2- and 5-year leukemia-free survival rates were 78% and 72%, indicating a promising long-term outcome despite treatment-related challenges.

The study highlighted significant treatment-related toxicities, including chronic graft-versus-host disease (cGVHD) in 30% of patients and pulmonary symptoms in 15.5%, while no acute or late cardiac toxicities or secondary malignancies were reported, suggesting a need for improved radiation techniques to minimize organ damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia. Marnitz, S., Zich, A., Martus, P., et al.[2021]

In a study of 326 patients with acute leukemia undergoing bone marrow transplantation (BMT) after total-body irradiation (TBI), the technique of TBI (single dose vs. fractionated) did not significantly affect survival rates or the incidence of complications.

However, the incidence of cataracts was significantly influenced by the instantaneous dose rate of TBI, with higher rates observed in patients receiving higher dose rates, highlighting the importance of dose management in minimizing long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Results and prognostic factors in 326 consecutive patients. Belkacémi, Y., Pène, F., Touboul, E., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12118588/

Efficacy of Total‐Body Irradiation‐based Intensified ... In this study, we compared outcomes of intensified myeloablative conditioning regimens using large registry data from Japan (Japanese Society ...

2. nature.com nature.com/articles/s41598-025-94556-3

Total body irradiation versus chemotherapy myeloablative ... Both TBI and chemotherapy regimens showed comparable overall survival (OS) and leukemia-free survival (LFS). However, TBI had a trend of reduced ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265024024467

Review Article Efficacy and Safety of Total Body Irradiation ... This systematic review and meta-analysis compare the efficacy of total body irradiation (TBI) versus chemotherapy (CHT) based regimens for conditioning in ...

4. astctjournal.org astctjournal.org/article/S2666-6367(20)30028-2/fulltext

Prognostic Impact of the Fractionation of Total Body ... This study compared 4- versus 6-fraction 12-Gy total body irradiation (TBI) for allogeneic hematopoietic cell transplantation in acute myeloid leukemia.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06803745

Standard-of-Care Reduced-Intensity Conditioning (RIC) ... The higher dose of TBI may increase the anti-cancer activity and the chance of engraftment, thereby reducing the patient's risk of disease ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11646108/

Long‐Term Outcomes of Reduced‐Toxicity Conditioning ... 8‐Gy TBI/FLU/CY RTC was safe in children with hematological malignancies, regardless of the donor source.

7. medrxiv.org medrxiv.org/content/10.1101/2024.11.16.24316211v1.full-text

Efficacy and Safety of Total Body Irradiation versus ... TBI as a conditioning regimen for ALL patients undergoing HSCT is associated with improved OS, EFS, and lower relapse rates than CHT-only myeloablative ...

8. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4865/492317/Long-Term-Data-Confirm-the-Superiority-of-Total

Long-Term Data Confirm the Superiority of Total Body ... Long-term data confirm the superiority of total body irradiation-containing conditioning regimen in comparison to a chemotherapy-based preparation.