Total Marrow Irradiation for Multiple Myeloma

(TMI-ASCT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Harold L Atkins, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Ottawa Hospital Research Institute

Must be taking: Intense corticosteroids

Disqualifiers: Non-secretory myeloma, Life expectancy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that conformal radiation will allow the administration of higher doses of external beam radiation to marrow based malignancies than total body irradiation (TBI)without increasing the toxicity to normal tissues beyond that induced by TBI. Further,the investigators hypothesize that this will result in an improvement in disease response and disease control for patients with multiple myeloma. This is a dose escalation study of TMI with the primary objective of determining the maximum tolerated dose of TMI when followed by aHSCT in patients with relapsed or refractory multiple myeloma.

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 Marrow Irradiation for Multiple Myeloma?

Research shows that Total Marrow Irradiation (TMI) can be a promising alternative to Total Body Irradiation (TBI) for patients with multiple myeloma, as it targets the bone marrow more precisely and spares other organs, potentially reducing side effects. Studies indicate that TMI can be safely combined with chemotherapy and stem cell transplantation, offering a viable option for patients with high-risk or relapsed blood cancers. ^{1 2 3 4 5}

Is total marrow irradiation safe for humans?

Total marrow irradiation (TMI) has been shown to be safely administered in various studies, with low rates of transplant-related mortality and manageable early side effects like oral mucositis (mouth sores) and gastrointestinal symptoms. It is considered a safer alternative to total body irradiation (TBI) as it targets the skeleton and spares other organs, but further studies are needed to monitor long-term safety. ^{2 6 7 8 9}

How is the treatment Total Marrow Irradiation (TMI) different from other treatments for multiple myeloma?

Total Marrow Irradiation (TMI) is unique because it targets the bone marrow specifically, sparing other organs from radiation exposure, unlike Total Body Irradiation (TBI) which affects the entire body. This targeted approach reduces side effects and allows for higher doses of radiation, potentially improving outcomes for patients with multiple myeloma. ^{2 3 4 5 10}

Research Team

Harold L Atkins, MD

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for adults aged 18-60 with relapsed or refractory multiple myeloma, who have measurable monoclonal gammopathy. They must have enough cryopreserved stem cells for transplantation and be in good enough health to undergo the procedure. Pregnant women, those with non-secretory myeloma or other plasma cell disorders, previous radiation treatments, severe concurrent illnesses, or a history of non-compliance are excluded.

Inclusion Criteria

My heart, kidneys, liver, and lungs are healthy enough for a stem cell transplant.

My multiple myeloma has not responded to initial treatment or has come back.

I am between 19 and 59 years old.

Exclusion Criteria

I have a plasma cell disorder that is not multiple myeloma.

Subjects with a history of non-compliance in other studies.

I haven't had intense corticosteroid treatment for my multiple myeloma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive Total Marrow Irradiation (TMI) as part of the dose escalation study to determine the maximum tolerated dose

4-6 weeks

Autologous Stem Cell Transplantation

Participants undergo autologous stem cell transplantation following TMI

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Total Marrow Irradiation (Radiation)

Trial Overview The study tests if Total Marrow Irradiation (TMI) can deliver higher doses to bone marrow malignancies compared to traditional methods without increasing toxicity. It's a dose escalation study aiming to find the maximum tolerated dose of TMI before autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Treatment with TMI and autologous Stem Cell transplant

Total Marrow Irradiation is already approved in Canada for the following indications:

Approved in Canada as Total Marrow Irradiation for:

• High-risk acute leukemia
• Myelodysplastic syndrome

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Dr. Kathleen Gartke

Ottawa Hospital Research Institute

Chief Medical Officer

MD, University of Ottawa

Dr. Rebecca Auer

Ottawa Hospital Research Institute

Chief Executive Officer

MD, Memorial Sloan-Kettering Cancer Centre

Findings from Research

In a phase 1 trial involving 13 patients with multiple myeloma, total marrow irradiation (TMI) combined with melphalan showed a low rate of acute toxicity, with only one dose-limiting toxicity observed at the 12 Gy dose level, indicating a good safety profile for this treatment approach.

After a median follow-up of 55 months, 70% of patients were alive, with 38.5% achieving a very good partial response and 30.8% achieving complete response, suggesting that TMI is effective in improving outcomes for patients at first relapse in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Study of the Combination of Escalated Total Marrow Irradiation Using Helical Tomotherapy and Fixed High-Dose Melphalan (140 mg/m²) Followed by Autologous Stem Cell Transplantation at First Relapse in Multiple Myeloma. Cailleteau, A., Maingon, P., Choquet, S., et al.[2023]

Total Marrow Irradiation (TMI) and Total Marrow and Lymphoid Irradiation (TMLI) are promising alternatives to traditional Total Body Irradiation (TBI) in hematopoietic cell transplantation, allowing for higher doses of targeted radiotherapy while minimizing damage to surrounding organs.

These techniques have been shown to be safely administered with low rates of transplant-related mortality, making them suitable for high-risk patients, including those with multiple myeloma and elderly or frail individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies. Kerbauy, MN., Arcuri, LJ., Favareto, SL., et al.[2023]

Using helical tomotherapy for total body irradiation (TBI) allows for significant sparing of normal organs while effectively targeting bone marrow and lymphatics, with a median dose reduction of 51% to organs at risk compared to traditional TBI methods.

This technique not only enables dose escalation but also potentially reduces the severity and frequency of late effects associated with radiation, such as pneumonitis and second tumors, by minimizing exposure to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy. Schultheiss, TE., Wong, J., Liu, A., et al.[2022]

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]

JP4-039, a novel radiation mitigator, was administered to mice after exposure to high doses of total-body irradiation (9.0 and 9.15 Gy) and demonstrated safety with no adverse effects on liver or kidney function, nor on survival rates.

The treatment with JP4-039 led to significant recovery of bone marrow cellularity and hematopoietic function by day 30, indicating its potential efficacy in promoting recovery after radiation exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome. Goff, JP., Epperly, MW., Dixon, T., et al.[2021]

References

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

Phase 1 Study of the Combination of Escalated Total Marrow Irradiation Using Helical Tomotherapy and Fixed High-Dose Melphalan (140 mg/m²) Followed by Autologous Stem Cell Transplantation at First Relapse in Multiple Myeloma. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies. [2023]

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

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy. [2022]

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

Organ sparing of linac-based targeted marrow irradiation over total body irradiation. [2023]

5. Ireland 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. [2012]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

Total marrow irradiation versus total body irradiation using intensity-modulated helical tomotherapy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety of total body irradiation using intensity-modulated radiation therapy by helical tomotherapy in allogeneic hematopoietic stem cell transplantation: a prospective pilot study. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Radiobiologic effects of GS-nitroxide (JP4-039) on the hematopoietic syndrome. [2021]

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

High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications. [2019]