Bone Marrow Transplant for Blood Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Pregnant, Active infection, HIV, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for performing bone marrow transplants in individuals with certain blood cancers, such as leukemia and lymphoma. It uses a special type of donor cells called HLA-haploidentical cells, sourced from a close family member, combined with a less intense preparation process. This process includes treatments like Fludarabine (a chemotherapy drug), Melphalan (another chemotherapy drug), and Total Body Irradiation, to determine if it helps patients remain disease-free for at least 18 months post-transplant. Suitable candidates have blood cancer in remission or cannot find a perfectly matched donor. 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 the combination of fludarabine, melphalan, and total body irradiation is generally well-tolerated by patients undergoing treatment for blood cancer. Fludarabine and melphalan are chemotherapy drugs, while total body irradiation uses radiation to prepare the body for a transplant.

Studies have found that this treatment combination helps the body accept the transplant and reduces cancer cells. Previous research highlights that the side effects of this approach are manageable. Patients often recover important blood cells, like neutrophils and platelets, within a few weeks after treatment. These cells are crucial for fighting infections and preventing bleeding.

While side effects such as tiredness, nausea, or a higher risk of infection can occur, these are common with treatments like this. Overall, the treatment shows promise in balancing effectiveness and tolerability. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this treatment because it combines Fludarabine, Melphalan, and Total Body Irradiation as a conditioning regimen before a bone marrow transplant. This combination aims to optimize the body's preparation for receiving new stem cells, potentially improving outcomes for patients with blood cancers. Unlike standard chemotherapy and radiation protocols, this approach utilizes a specific cocktail of drugs and total body irradiation to better target cancer cells while reducing the risk of rejection. By using HLA-haploidentical related hematopoietic cells, this method could make bone marrow transplants more accessible to patients who might not have a fully matched donor.

What evidence suggests that this treatment might be an effective treatment for blood cancers?

In this trial, all participants will receive a conditioning regimen of fludarabine, melphalan, and total body irradiation (TBI) before transplantation. Research has shown that this combination effectively treats blood cancers. Studies have found that patients who received this treatment often experienced positive outcomes, with many recovering important blood cells like neutrophils and platelets within 56 days. Additionally, donor cells began to grow and function reliably in the patient's body within the first few months after treatment. This treatment plan is generally well-tolerated, even for patients receiving transplants from donors who are not a perfect match. Overall, evidence supports that this combination improves disease-free survival in blood cancer patients. ^{4 6 7 8 9}

Who Is on the Research Team?

Nelli Bejanyan, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 55+ or with certain health conditions, lacking a fully matched sibling donor, and with specific blood cancers in remission or sensitive to chemotherapy. They must have good organ function, agree to birth control if applicable, and have an HLA-haploidentical relative as a donor.

Inclusion Criteria

I am mostly able to care for myself and carry out daily activities.

My condition is related to natural killer cell malignancies.

I have CML in the accelerated phase and TKIs haven't worked for me or I can't tolerate them.

Exclusion Criteria

I am currently living with HIV.

I have had a bone marrow transplant from a donor or my own within the last 6 months.

I have an active brain or spinal cord tumor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen of Fludarabine, Melphalan, and Total Body Irradiation prior to transplantation

1-2 weeks

Transplantation

Transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT)

1 day

Follow-up

Participants are monitored for safety and effectiveness after transplantation

18 months

What Are the Treatments Tested in This Trial?

Interventions

• Fludarabine
• Melphalan
• Total Body Irradiation

Trial Overview The study tests a transplant of blood cells from half-matched relatives using lower doses of Fludarabine and Melphalan drugs plus whole-body radiation. The goal is to see how many patients are disease-free after 18 months.

How Is the Trial Designed?

Group I: Conditioning Regimen + Transplant Experimental Treatment 3 Interventions

All participants will receive a conditioning regimen of Fludarabine, Melphalan and Total Body Irradiation prior to transplantation of HLA-Haploidentical Related Hematopoietic Cells (Haplo-HCT)

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?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

In a study of 394 acute myeloid leukemia patients undergoing allogeneic stem cell transplantation, the fludarabine plus melphalan (FM) regimen showed a significantly lower relapse incidence compared to fludarabine plus busulfan (FB), indicating better control of the disease.

Despite the differences in relapse rates, both FM and FB regimens resulted in similar overall survival rates, suggesting that while FM may be more effective in preventing relapse, both treatments are comparably effective in terms of long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Baron, F., Labopin, M., Peniket, A., et al.[2015]

The addition of total body irradiation (TBI) and a reduction in melphalan dosage in the FluMelTBI-75 regimen led to improved overall survival (OS) and progression-free survival (PFS) compared to the standard FluMel regimen, based on a phase II trial involving 94 patients.

FluMelTBI-75 was better tolerated, showing a significant reduction in stomatitis and improved disease control for patients not in complete remission at the time of transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-Intensity Conditioning with Fludarabine, Melphalan, and Total Body Irradiation for Allogeneic Hematopoietic Cell Transplantation: The Effect of Increasing Melphalan Dose on Underlying Disease and Toxicity. Chen, GL., Hahn, T., Wilding, GE., et al.[2022]

In a study of 85 patients with hematological malignancies, adding fludarabine to a 2-Gy total body irradiation (TBI) regimen before stem cell transplantation resulted in better overall survival (65% vs. 54%) and lower relapse rates compared to TBI alone.

The combination of fludarabine and TBI led to significantly higher levels of donor T cell and NK cell chimerism, indicating improved donor engraftment and a stronger graft-versus-tumor effect, which is crucial for successful transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Kornblit, B., Maloney, DG., Storb, R., et al.[2021]

The combination of fludarabine and melphalan with total body irradiation (Flu-Mel140-TBI) in 81 patients undergoing allogeneic stem cell transplantation showed a 3-year overall survival rate of 39.81%, indicating that this regimen is feasible and can provide durable disease control.

Despite the addition of TBI, there was no significant improvement in outcomes compared to previous reports of Flu-Mel140 alone, and the study highlighted considerable non-relapse mortality (29.9%) particularly in older patients and those with prior transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation. Modi, D., Chi, J., Kim, S., et al.[2021]

In a study of 31 patients with hematologic malignancies who were poor candidates for total body irradiation (TBI), the fludarabine-melphalan regimen resulted in successful engraftment for all patients, indicating its efficacy in stem cell transplantation.

However, the treatment was associated with significant regimen-related toxicities, including renal, hepatic, and mucosal issues, leading to seven regimen-related deaths, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regimen-related toxicity after fludarabine-melphalan conditioning: a prospective study of 31 patients with hematologic malignancies. Van Besien, K., Devine, S., Wickrema, A., et al.[2013]

The addition of 9 Gy of total body irradiation (TBI) to a reduced intensity regimen of fludarabine and melphalan in pediatric patients with advanced hematologic malignancies resulted in successful neutrophil and platelet engraftment, with 27 patients achieving neutrophil engraftment by a median of 16 days.

Despite some toxicities like oral mucositis and diarrhea, the treatment was generally well tolerated, and with a median follow-up of 52 months, 7 out of 22 patients with acute lymphoblastic leukemia (ALL) and 5 out of 6 patients with acute myeloid leukemia (AML) remained alive and in remission, indicating potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies. Petropoulos, D., Worth, LL., Mullen, CA., et al.[2013]

In a study of 21 patients undergoing non-myeloablative conditioning chemotherapy with melphalan and fludarabine before allogeneic stem cell transplantation, three patients developed severe left ventricular failure, indicating a potential risk of cardiotoxicity with this treatment combination.

This finding is significant as cardiotoxicity from melphalan and fludarabine has not been previously reported, highlighting the need for careful assessment and monitoring of cardiac health in patients receiving this pre-transplant regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute left ventricular failure following melphalan and fludarabine conditioning. Ritchie, DS., Seymour, JF., Roberts, AW., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33991722/

Outcomes of Fludarabine, Melphalan and Total Body ... We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell ...

2. astctjournal.org astctjournal.org/article/S1083-8791(18)30609-8/fulltext

The Effect of Increasing Melphalan Dose on Underlying ... Less robust patients with residual malignant disease may benefit most from fludarabine (160 mg/m2), melphalan (75 mg/m2), and total body irradiation. ABSTRACT.

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/87/NCT04191187/Prot_SAP_000.pdf

Reduced-Intensity Fludarabine, Melphalan, and Total Body ... Incidence of neutrophil recovery by day +56. • Incidence of platelet recovery by day +56. • Donor cell engraftment (chimerism) at day +30, +60, +90, ...

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

Total Body Irradiation and Fludarabine with Post- ... Total body irradiation- and fludarabine-based myeloablative conditioning regimen was well tolerated in mismatched related and unrelated donor HCT recipients.

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)40019-5/fulltext

905P Outcomes of fludarabine, melphalan and low dose ... We retrospectively evaluated efficacy and long-term outcomes of pts undergoing either 8/8 HLA-matched unrelated (MUD) (n=60) or related (MRD) (n=24) donor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00856388?cond=%22Follicular%20Lymphoma%22&intr=%22Thymoglobulin%22&viewType=Table&rank=10

Study Details | Fludarabine Phosphate, Melphalan, Total-Body ... This clinical trial is studying how well giving fludarabine phosphate and melphalan together with total-body irradiation followed by donor stem cell ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7101620/

Single center experience with total body irradiation and ... We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1200 cGy) and melphalan (MEL) (100–110 mg/m2) ...

8. astctjournal.org astctjournal.org/article/S1083-8791(17)30761-9/fulltext

Total Marrow Lymphoid Irradiation/Fludarabine/ Melphalan ... Outcomes compare favorably with those associated with reduced-intensity conditioning regimens. Abstract. Reduced-intensity conditioning (RIC) regimens for ...

9. ashpublications.org ashpublications.org/blood/article/101/4/1620/105963/Low-dose-total-body-irradiation-TBI-and

Low-dose total body irradiation (TBI) and fludarabine followed ... Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors ...