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

Trial Summary

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 data supports the effectiveness of the treatment Total Body Irradiation for Acute Leukemia?

Research shows that patients with acute leukemia who received total body irradiation (TBI) as part of their treatment had better two-year survival rates (77%) compared to those who did not receive TBI (51%). Additionally, the relapse rate was lower in the TBI group (16%) compared to the non-TBI group (37%). ^{1 2 3 4 5}

Is total body irradiation safe for humans?

Total body irradiation (TBI) has been used in treating acute leukemia, and studies have looked at both early and late side effects. Some patients may experience complications like interstitial pneumonitis (lung inflammation), but TBI can also help reduce the risk of leukemia returning. Overall, TBI is considered a part of treatment regimens, with safety data showing both risks and benefits. ^{3 4 5 6 7}

How is total body irradiation treatment different for acute leukemia?

Total body irradiation (TBI) is unique because it involves exposing the entire body to radiation to prepare patients for bone marrow transplantation, which helps reduce the risk of leukemia returning. Unlike other treatments, TBI is often used in combination with chemotherapy to improve survival rates and reduce relapse in patients with acute leukemia. ^{4 5 8 9 10}

What is the purpose of this trial?

This is a randomized phase II trial of standard-of-care reduced-intensity conditioning (RIC) with 200 versus 400 cGy of total body irradiation (TBI) in patients with acute leukemia undergoing first allogeneic blood or marrow Transplantation (BMT). The primary objective is to compare the rates of graft-versus-host disease-free and relapse-free survival (GRFS) between patients in the two cohorts.

Research Team

Jonathan Webster

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

[Radiobiologic considerations about further development of whole-body irradiation with subsequent bone marrow transplantation applied during the treatment of acute leukemia (author's transl)]. [2006]

3. Germany pubmed.ncbi.nlm.nih.gov

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Magna-field irradiation: work in progress in bone marrow transplantation at The Princess Margaret Hospital, Toronto. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Treatment Complications and Long-term Outcomes of Total Body Irradiation in Patients with Acute Lymphoblastic Leukemia: A Single Institute Experience. [2022]

7. Germany 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. [2023]

8. Italy pubmed.ncbi.nlm.nih.gov

[Total body irradiation in the preparation of leukemic patients for bone marrow transplantation]. [2008]

9. United States pubmed.ncbi.nlm.nih.gov

Fractionated or single-dose total body irradiation in 171 acute myeloblastic leukemias in first complete remission: is there a best choice? SFGM. Société Française de Greffe de Moelle. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Physical aspects of total body irradiation in Basel. [2004]