Targeted Total Marrow Irradiation for Leukemia

Overseen By Rondelli Damiano, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Disqualifiers: Cirrhosis, Low ejection fraction, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to prepare patients with certain types of leukemia and myelodysplastic syndromes for a bone marrow transplant. The approach combines targeted total marrow irradiation (a focused radiation treatment) with other medicines to prevent post-transplant complications. Individuals with difficult-to-treat or relapsed leukemia, or those with specific genetic risk factors, may qualify if they have a related donor with a partial HLA match. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that total marrow irradiation (TMI) might be safer than traditional total body irradiation (TBI). One study found that TMI reduces radiation exposure to important organs, potentially leading to fewer side effects from radiation therapy.

Another study found that using TMI before a stem cell transplant could be an effective alternative with positive results. Patients tolerated the treatment well, indicating good safety.

Overall, these studies suggest that TMI is generally well-tolerated and has fewer side effects compared to other radiation methods. This makes it a promising option for patients considering clinical trials involving TMI. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for leukemia, which typically involves broad radiation therapy or chemotherapy, Total Marrow Irradiation (TMI) is unique because it specifically targets the marrow where leukemia cells reside. This precision aims to minimize damage to surrounding healthy tissues and reduce side effects commonly associated with traditional treatments. Researchers are excited about TMI because it has the potential to be more effective at eliminating cancer cells while preserving the patient's quality of life by sparing healthy organs.

What evidence suggests that targeted total marrow irradiation might be an effective treatment for leukemia?

Research has shown that Total Marrow Irradiation (TMI), studied in this trial, can help prepare leukemia patients for a bone marrow transplant. One study found that TMI reduces radiation exposure to healthy organs compared to Total Body Irradiation (TBI). Another study demonstrated that TMI is safe and effective for patients with recurring leukemia, leading to better outcomes. Specifically, patients who received a certain TMI dose achieved complete remission in up to 100% of cases, with over 55% surviving for at least one year. These findings suggest that TMI may offer better tumor control and safer results for leukemia patients undergoing transplants. ^{2 4 6 7 8}

Who Is on the Research Team?

Rondelli Damiano, MD

Principal Investigator

University of Illinois at Chicago

Are You a Good Fit for This Trial?

Adults aged 18-75 with certain types of leukemia or myelodysplastic syndrome, who haven't responded well to other treatments and need frequent transfusions. They must have a related donor that's at least half-matched genetically, or an unrelated donor with specific mismatches. Participants should be in decent health otherwise, without serious liver issues or heart and lung function below half the normal level.

Inclusion Criteria

My vital organs are functioning well.

My cancer has specific genetic features considered high-risk.

Presentation WBC >30 × 109 for B-ALL or >100 109 for T-ALL

Exclusion Criteria

My health is significantly impaired; I need assistance for self-care.

You have other health problems that could interfere with the study.

I have a history of cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Patients receive a conditioning regimen with fludarabine, cyclophosphamide, and total body irradiation, including targeted total marrow irradiation (TMI) at a dose of 6Gy

2 weeks

Transplantation

Haploidentical hematopoietic stem cell transplant (HSCT) is performed

1 week

Post-transplant Prophylaxis

Graft-versus-host disease prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including engraftment rates and donor chimerism at day 30

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Mycophenolate Mofetil
• Tacrolimus
• Total Marrow Irradiation

Trial Overview The trial is testing a pre-transplant conditioning process using targeted total marrow irradiation (TMI) at a dose of 6Gy. After transplant, patients will receive cyclophosphamide along with tacrolimus and mycophenolate mofetil to prevent graft-versus-host disease.

Total Marrow Irradiation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Total Marrow Irradiation for:

• High-risk acute leukemia
• Myelodysplastic syndrome

Approved in European Union as Total Body Irradiation for:

• Acute leukemia
• Myelodysplastic syndrome
• Lymphoma

Approved in Canada as Total Marrow Irradiation for:

• High-risk acute leukemia
• Myelodysplastic syndrome

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Published Research Related to This Trial

Total body irradiation (TBI) is commonly used in conditioning regimens for hematopoietic stem cell transplantation but carries significant risks of side effects like pulmonary toxicity and second malignancies.

Total marrow irradiation (TMI) is a newer technique that allows for targeted radiation to the bone marrow, potentially delivering higher doses while reducing overall toxicity, paving the way for more personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Status and Perspectives of Irradiation-Based Conditioning Regimens for Patients with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation. Potdar, RR., Gupta, S., Giebel, S., et al.[2021]

In a study of 37 patients receiving total marrow irradiation (TMI) before hematopoietic stem cell transplantation (HSCT), TMI demonstrated a 1-year graft-versus-host disease-free, relapse-free survival (GRFS) rate of 67.5%, which is significantly better than historical data for total body irradiation (TBI).

TMI resulted in faster engraftment of platelets compared to TBI, with a low occurrence of treatment-related toxicities, suggesting that TMI may be a safer and effective alternative to TBI in myeloablative conditioning for HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ sparing total marrow irradiation compared to total body irradiation prior to allogeneic stem cell transplantation. Haraldsson, A., Wichert, S., Engström, PE., et al.[2022]

In a study involving 15 patients with relapsed acute leukemia, the combination of total body irradiation (TBI) followed by total marrow irradiation (TMI) was found to be clinically feasible, with all patients achieving complete remission after stem cell transplant.

TMI significantly reduced radiation exposure to surrounding organs by 30% to 65%, while maintaining effective targeting of bone marrow, suggesting it may enhance treatment efficacy with a lower risk of severe side effects compared to conventional TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant. Corvò, R., Zeverino, M., Vagge, S., et al.[2012]

In a study of 109 pediatric patients treated with total body irradiation (TBI) before stem cell transplantation for leukemia, the overall survival rates were high, with 63% surviving at 10 years, indicating the efficacy of TBI in this context.

Despite the effectiveness of TBI, 43% of patients experienced long-term toxicities, including growth retardation and abnormal liver and kidney function, highlighting the need for improved treatment techniques and long-term follow-up to manage these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies. Gruen, A., Exner, S., Kühl, JS., et al.[2022]

Using 24 MV photons for total-body irradiation (TBI) in bone marrow transplantation helps achieve a more uniform radiation dose distribution, which reduces the risk of organ injury to the lungs, liver, and kidneys in patients with high-risk leukemias.

The study found that while TBI increased bone marrow dose due to interactions with bone, the overall treatment regimen effectively minimized end-organ toxicities, making it a safer option for patients undergoing transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications. Bradley, J., Reft, C., Goldman, S., et al.[2019]

Higher biologically effective doses (BEDs) of total-body irradiation (TBI) during hematopoietic stem cell transplantation significantly reduce relapse incidence and improve overall survival, based on a review of multiple studies.

While increasing the dose improves outcomes, it is crucial to manage the BED to minimize damage to vital organs like the lungs, kidneys, and eye lenses, ensuring patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation. Kal, HB., Loes van Kempen-Harteveld, M., Heijenbrok-Kal, MH., et al.[2018]

Total marrow irradiation (TMI) significantly reduces radiation exposure to critical organs such as the liver, kidneys, and lungs compared to total body irradiation (TBI), achieving up to a 59% reduction in kidney dose while maintaining the necessary dose to the targeted skeletal area.

TMI not only protects organs at risk more effectively but also decreases the treatment time by an average of 217 seconds, making it a potentially safer and more efficient alternative to TBI for patients undergoing hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total marrow irradiation versus total body irradiation using intensity-modulated helical tomotherapy. Köksal, M., Kersting, L., Schoroth, F., et al.[2023]

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]

Targeted marrow irradiation (TMI) maintains effective coverage of the clinical target volume (CTV) for patients undergoing bone marrow transplantation, similar to total body irradiation (TBI), but with improved dose distribution.

TMI significantly spares critical organs such as the lungs, brain, kidneys, and liver, reducing their radiation exposure by up to 55%, which may allow for higher doses to the target area or more frequent treatments without increasing tissue complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Organ sparing of linac-based targeted marrow irradiation over total body irradiation. Warrell, GR., Colussi, VC., Swanson, WL., et al.[2023]

Myeloablative Total Body Irradiation (TBI) is primarily used for conditioning in high-risk acute lymphoblastic leukemia (ALL) patients, but it is not recommended for children under 3-4 years old due to higher toxicity risks.

The recommended TBI dose for children is between 12-14.4 Gy, with specific dose reductions for sensitive organs, and advanced techniques like TomoTherapy and VMAT TBI are encouraged to improve safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ESTRO ACROP and SIOPE recommendations for myeloablative Total Body Irradiation in children. Hoeben, BAW., Pazos, M., Seravalli, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10356893/

Total marrow irradiation versus total body irradiation using ... Our study shows that the use of TMI instead of TBI in the conditioning regimen prior to HSCT allows a significant radiation dose reduction in OARs.

2. reporter.nih.gov reporter.nih.gov/project-details/10783685

Conformal Total Body and Marrow Irradiation for Leukemia This project is designed to provide improved tumor control and safe outcomes by discovering optimal dose escalation strategies.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723012460

Total Marrow Irradiation for Second Allogeneic ... This retrospective study demonstrates the safety and efficacy of a hypofractionated TMI conditioning regimen in patients with acute leukemia undergoing second ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1003908/full

Total marrow irradiation (TMI): Addressing an unmet need ... These patients have a dismal outcome after HCT with a long-term survival of 16% to 19% (31). Patients with acute leukemia who relapse after first remission are ...

5. astctjournal.org astctjournal.org/article/S1083-8791(17)30192-1/fulltext

Phase I Trial of Total Marrow and Lymphoid Irradiation ... The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall 1-year survival was 55.5% (95% CI, 40.7 to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7708691/

The safety and efficacy of a novel hypo-fractionated total ... Our results first showed TMLI (8–10 Gy/2F) could be an acceptable alternative with encouraging OS. Keywords: Helical tomotherapy, Allogeneic ...

7. 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02094794

Total Marrow and Lymphoid Irradiation and Chemotherapy ... This phase II trial studies the safety and efficacy of total marrow and lymphoid irradiation (TMLI) in combination with two chemotherapy drugs, ...