Fludarabine and TBI for Blood Cancers

Overseen By Caitlin Guzowski

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northside Hospital, Inc.

Disqualifiers: Poor cardiac, pulmonary, liver, renal function, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for people with blood cancers who need a stem cell transplant from a family member. It examines the safety and effectiveness of a specific process using lower doses of chemotherapy (fludarabine) and radiation (Total Body Irradiation, TBI) before a transplant. The goal is to assist patients at high risk of cancer returning after other treatments. Candidates may qualify if they have a blood cancer requiring a transplant and a family member who can donate stem cells. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants the chance to be part of a potentially groundbreaking therapy.

Do I need to stop my current medications for the trial?

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 this transplant protocol is safe?

Research has shown that the safety of using fludarabine and total body irradiation (TBI) in certain transplant treatments is generally well-documented. Studies have found that TBI-based treatments, which the researchers are exploring, have survival rates similar to other types of transplants, with comparable chances of relapse and complications like graft-versus-host disease (GVHD). GVHD occurs when the donor's cells attack the recipient's body.

For fludarabine, results are mixed. Some studies found no transplant-related deaths in certain situations, while others noted concerns about early deaths when used in different combinations. This indicates that the safety of fludarabine can depend on its combination with other treatments.

Overall, while both fludarabine and TBI have shown promise in past studies, their safety can vary based on the specific treatment combination and the patient's condition. Anyone considering this trial should consult with their healthcare provider to understand what these findings mean for their personal situation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using reduced intensity fludarabine and TBI before haplo-identical transplantation because they offer a potentially less toxic approach compared to traditional high-dose conditioning regimens. Unlike standard treatments that use high doses of chemotherapy and radiation, this method aims to minimize harmful side effects while still effectively preparing the body for a stem cell transplant. By using a lower intensity regimen, there's hope for better patient tolerance and more successful transplant outcomes, especially for those who may not withstand the rigors of conventional treatment.

What evidence suggests that this protocol is effective for transplantation?

Research has shown that using fludarabine with haplo-identical transplantation can yield positive results. In patients with serious conditions, fludarabine-based treatments have significantly improved survival rates. One study found that after one year, up to 81.8% of patients remained free from complications and disease relapse.

Regarding total body irradiation (TBI) combined with haplo-identical transplantation, the results are also promising. Studies have reported a one-year disease-free survival rate of 51% for patients receiving TBI-based treatments. Additionally, these treatments facilitate quick recovery and good long-term survival. ^{3 6 7 8 9}

Who Is on the Research Team?

Scott Solomon, MD

Principal Investigator

BMTGA

Are You a Good Fit for This Trial?

Inclusion Criteria

Availability of 3/6 - 5/6 matched related donor with a negative HLA-cross match in the host vs. graft direction willing to donate peripheral blood stem cells

KPS >/= 70%

Hematologic malignancy requiring allogeneic transplantation, with a predicted high risk of relapse following non-myeloablative, low intensity conditioning.

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 fludarabine and total body irradiation (TBI) 800 cGy

1-2 weeks

Transplantation

Haplo-identical transplantation using peripheral blood stem cells (PBSC) is performed

1 week

Follow-up

Participants are monitored for safety and effectiveness after transplantation

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fludarabine
• Haplo-Identical Transplantation
• Total Body Irradiation (TBI)

Fludarabine is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Fludara for:

• Chronic lymphocytic leukemia
• Mantle-cell lymphoma
• Non-Hodgkin's lymphoma

Approved in United States as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma
• Stem Cell Transplant Conditioning

Approved in Canada as Fludara for:

• Chronic lymphocytic leukemia
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

Northside Hospital, Inc.

Lead Sponsor

Trials

26

Recruited

1,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5663557/

Improved outcome of haploidentical transplantation in severe ... Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/510/530868/Low-Dose-Fludarabine-Is-an-Effective-Conditioning

Low Dose Fludarabine Is an Effective Conditioning Treatment ... The two-year GVHD-free, relapse-free survival (GRFS) significantly increased in the 3-day fludarabine group (55%) compared with 5-day ...

3. astctjournal.org astctjournal.org/article/S1083-8791(15)00685-0/fulltext

Outcomes of Haploidentical Stem Cell Transplantation for ... Sixty-eight percent of all patients were not in complete remission at the time of transplantation. The 2-year progression-free survival (PFS) and overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724005852

Total Body Irradiation and Fludarabine with Post- ... In this retrospective study, we investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11368812/

Efficacy and safety of outpatient fludarabine ... Results showed a 100% survival rate at a median follow-up of 302 days, as well as a 1-year GVHD-free/relapse-free survival (GRFS) rate of 81.8%, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1083879119303817

Fludarabine and Total-Body Irradiation Conditioning before ... Fludarabine and Total-Body Irradiation Conditioning before Ablative Haploidentical Transplantation: Long-Term Safety and Efficacy.

7. astctjournal.org astctjournal.org/article/S2666-6367(24)00585-2/fulltext

Total Body Irradiation and Fludarabine with Post- ... We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT (related/haploidentical versus unrelated [MMUD]) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05417971

Reduced Intensity Fludarabine and TBI Prior to Haplo ... This trial will evaluate the safety and efficacy of RIC HIDT transplant protocol following fludarabine and intermediate-dose TBI 800 cGy utilizing PBSC as the ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2021.1978087

Increased early mortality after fludarabine and melphalan ... The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the ...