Stem Cell Transplant with Conditioning Regimen for Blood Diseases

Overseen By Lauri Burroughs

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: Idiopathic aplastic anemia, Fanconi anemia, 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: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new, less intense method to prepare patients with non-cancerous blood diseases for stem cell transplants. The goal is to determine if using milder chemotherapy drugs can still enable healthy donor cells to replace the patient's faulty bone marrow without increasing side effects. This approach offers promise for individuals with conditions like immune disorders or bone marrow failure who seek a treatment that is potentially less taxing on their body. Ideal participants are those diagnosed with a non-cancerous blood disease that could be treated by a stem cell transplant (Allogeneic Hematopoietic Stem Cell Transplantation). As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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?

Studies have shown that the treatments tested in this clinical trial have varying safety levels. Treosulfan has proven safe and effective for various blood disorders, with some research indicating fewer serious side effects compared to similar drugs.

Fludarabine phosphate, another drug in the trial, can cause low blood cell counts, but these effects usually resolve. Rare but serious skin reactions have been reported.

Rabbit anti-thymocyte globulin (rATG) has lowered the risk of death in some studies, though it may increase the chance of infections from certain viruses.

Thiotepa has been used safely in other treatments, but it may cause irritation if it contacts the skin or is inhaled.

The stem cell transplant procedure itself carries risks like immune system problems, but extensive research supports its safety as a well-established procedure. Discuss any concerns with the study team, who can provide detailed information based on individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it combines a unique conditioning regimen with a stem cell transplant for blood diseases. Unlike traditional chemotherapy alone, this approach uses a combination of drugs like fludarabine phosphate, thiotepa, treosulfan, and rabbit anti-thymocyte globulin to prepare the body for the transplant. This combination aims to reduce the risk of graft-versus-host disease and improve the success rate of the transplant. By using a more targeted and intensive conditioning regimen, researchers hope to enhance patient outcomes compared to standard therapies.

What evidence suggests that this conditioning regimen is effective for nonmalignant blood diseases?

Research has shown that using donor cells for stem cell transplants can help treat non-cancerous blood diseases. In this trial, participants will receive a conditioning regimen that includes Treosulfan, which has demonstrated good long-term results and fewer side effects compared to drugs like busulfan. Thiotepa, another drug in the treatment plan, has been linked to higher survival rates in some studies. Fludarabine phosphate is effective and well-tolerated, leading to good response rates. Rabbit anti-thymocyte globulin (rATG) is also part of the regimen and has been used successfully to improve survival rates. Together, these treatments prepare the body for new healthy cells and aim to improve overall outcomes. ^{4 6 7 8 9}

Who Is on the Research Team?

Lauri Burroughs

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients under 50 with non-cancerous blood diseases or conditions like immune disorders, who haven't found a genetic cause for their illness. They need a matching donor for stem cell transplant and must not have severe heart, lung, kidney issues, HIV, active hepatitis or be pregnant.

Inclusion Criteria

My preferred cell source for donation is bone marrow, but peripheral blood stem cells may be used if needed.

My bone marrow graft meets the required cell count.

My donor matches me closely in immune system markers or has only one mismatch.

Exclusion Criteria

My lung function is significantly reduced, as shown by tests or oxygen levels below 92%.

Active infectious disease requiring deferral of conditioning as recommended by an infectious disease specialist

I am a donor without active infectious hepatitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive thiotepa, treosulfan, fludarabine phosphate, and rabbit anti-thymocyte globulin as conditioning therapy before transplantation

7 days

Daily visits for drug administration

Transplantation

Patients undergo allogeneic hematopoietic cell transplant via infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for engraftment and other outcomes

1 year

Annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation
• Fludarabine Phosphate
• Rabbit Anti-Thymocyte Globulin
• Thiotepa
• Treosulfan

Trial Overview The study tests a less toxic conditioning regimen before stem cell transplantation using drugs treosulfan, thiotepa, fludarabine phosphate and rATG to treat non-malignant diseases by replacing faulty bone marrow with healthy donor cells.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, transplant) Experimental Treatment 9 Interventions

Patients receive thiotepa IV BID over 2 hours on day -7, treosulfan IV over 120 minutes on days -6 to -4, fludarabine phosphate IV over 60 minutes on days -6 to -2, and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -2. Patients then undergo allogeneic hematopoietic cell transplant via infusion on day 0. Patients may also undergo bone marrow biopsy and aspiration and MRI as clinically indicated and blood sample collection on study.

Allogeneic Hematopoietic Stem Cell Transplantation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Canada as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Approved in Japan as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Primary immunodeficiency disorders
• Immune dysregulatory disorders
• Hemophagocytic lymphohistiocytosis
• Bone marrow failure syndromes
• Hemoglobinopathies

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Published Research Related to This Trial

In a study of 30 patients undergoing matched sibling or alternative donor transplantation with a conditioning regimen of fludarabine, thiotepa, and total body irradiation, most patients achieved prompt engraftment, but there were significant complications, including regimen-related toxicity leading to 18 deaths.

The 12-month progression-free survival rates were 47% for HLA-identical sibling transplants and 30% for all patients, but due to high rates of complications and relapses, the researchers decided to discontinue this conditioning regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and outcome after fludarabine-thiotepa-TBI conditioning for allogeneic transplantation: a prospective study of 30 patients with hematologic malignancies. van Besien, K., Devine, S., Wickrema, A., et al.[2013]

The addition of rabbit antithymocyte globulin to a low-dose conditioning regimen before hematopoietic stem cell transplantation may reduce the risk of graft-versus-host disease (GVHD), as indicated by a 40% incidence of acute GVHD in the study of 22 patients with hematologic malignancies.

Despite one case of graft rejection, the overall approach appears effective, with chronic GVHD developing in 9 of 14 patients who survived beyond 100 days, suggesting that this regimen can support successful transplantation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unrelated donor hematopoietic stem cell transplantation for patients with hematologic malignancies using a nonmyeloablative conditioning regimen of fludarabine, low-dose total body irradiation, and rabbit antithymocyte globulin. Rowley, SD., Goldberg, SL., Pecora, AL., et al.[2013]

A new phase II study with a reduced-toxicity conditioning regimen for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients showed significantly improved overall survival (96.7%) and event-free survival (93.3%) compared to a previous regimen (67.9% OS and 64.3% EFS).

The new regimen, which included lower doses of cyclophosphamide (Cy) and a modified schedule for fludarabine (FLU) and antithymocyte globulin (ATG), achieved successful hematologic recovery in all patients, indicating it may be a safer and more effective option for HSCT with unrelated donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Outcome of a Reduced Toxicity-Fludarabine, Cyclophosphamide, plus Antithymocyte Globulin Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia: Comparison of 2 Multicenter Prospective Studies. Kang, HJ., Hong, KT., Lee, JW., et al.[2018]

In a study involving three children with refractory severe aplastic anemia (SAA), a radiotherapy-free conditioning regimen using fludarabine and other agents was effective in preparing them for hemopoietic cell transplantation (HCT) without the development of graft-versus-host disease (GVHD).

All patients achieved normal blood counts and complete donor chimerism after the transplant, demonstrating that fludarabine-based conditioning can be a safe and effective option for children undergoing HCT from alternative donors, even after previous transplant failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Urban, C., Benesch, M., Sykora, KW., et al.[2013]

In a study of 80 patients undergoing haploidentical stem cell transplantation, a thiotepa-based conditioning regimen showed low toxicity and effective protection against severe graft-versus-host disease (GVHD), with cumulative incidences of only 16% for acute GVHD grade III to IV and severe chronic GVHD.

The overall survival rate at 2 years was 53%, and the disease-free survival rate was 47%, indicating that this modified regimen is effective for both patients in complete remission and those with relapsed/refractory malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies. Peric, Z., Mohty, R., Bastos, J., et al.[2023]

In a study involving 31 patients with nonmalignant diseases, a conditioning regimen using treosulfan and fludarabine resulted in 100% engraftment and a 0% early transplant-related mortality (TRM) at 100 days, indicating a safe and effective approach for hematopoietic cell transplantation.

The combination of treosulfan, fludarabine, and thymoglobulin led to a 90% survival rate over two years, with significantly lower rates of severe acute graft-versus-host disease (GVHD) in patients who received thymoglobulin, suggesting improved outcomes and reduced toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treosulfan-based conditioning and hematopoietic cell transplantation for nonmalignant diseases: a prospective multicenter trial. Burroughs, LM., Nemecek, ER., Torgerson, TR., et al.[2021]

The new conditioning regimen using thiotepa and fludarabine (TT-FLUDA) was well tolerated in six patients undergoing allogeneic bone marrow transplantation, with successful engraftment and stable donor chimerism in most cases.

Despite the patients being poor candidates for standard treatments, the TT-FLUDA regimen showed no major toxicity, although one patient died from acute graft-versus-host disease (GVHD), indicating a need for careful monitoring of GVHD prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant. Alessandrino, EP., Bernasconi, P., Colombo, AA., et al.[2019]

The combination treatment of treosulfan, thiotepa, and fludarabine was well tolerated in 20 thalassaemia patients undergoing allogeneic marrow transplantation, with low rates of transplantation-related mortality (5%) and graft failure (11%).

The two-year survival probability was high at 95%, and thalassaemia-free survival was 85%, suggesting that this regimen could be beneficial for patients at high risk of severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. Bernardo, ME., Zecca, M., Piras, E., et al.[2013]

In a study involving five patients with severe aplastic anemia, a conditioning regimen of fludarabine, cyclophosphamide, and thymoglobulin resulted in complete donor type hematologic recovery for all participants, indicating high efficacy for bone marrow transplantation.

The combination treatment showed minimal complications, with only one case of mild acute graft-versus-host disease (GVHD) and no serious complications, suggesting a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. Kang, HJ., Shin, HY., Choi, HS., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11503301/

Outcome of Allogeneic Hematopoietic Stem Cell ... Considering disease status at transplantation, the survival data are as follows: 37 patients alive out of 49 (76%) among CR1 patients, 7 out ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2943393/

Allogeneic hematopoietic cell transplantation: the state of ... Early rather than late allogeneic HCT was not only associated with better outcomes but also a decrease in the likelihood of complications that preclude HCT ( ...

3. astctjournal.org astctjournal.org/article/S2666-6367(24)00842-X/fulltext

Outcomes of Allogeneic Hematopoietic Stem Cell ... Allo-HCT provides promising outcomes for patients aged 70 or older with transplant-eligible diseases. Disease progression, followed by infections, is the ...

4. nature.com nature.com/articles/s41598-025-05602-z

Clinical outcomes of allogeneic hematopoietic stem cell ... This study emphasizes the efficacy of HSCT in the treatment of infant AML, with higher OS rates compared to childhood AML. It also supports UCB as a viable ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2697528/

Fludarabine in the treatment of chronic lymphocytic leukemia FAMP as a single agent has produced superior response rates and progression-free survival than standard therapy with chlorambucil and alkylator-based regimen.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5345733/

Safety and efficacy of allogeneic hematopoietic stem cell ... In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which ...

7. astctjournal.org astctjournal.org/article/S2666-6367(25)01447-2/fulltext

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... Allo-HSCT in SCD has OS, EFS, and mortality rates of 94%, 86% and 6%, respectively. •. NMA conditioning has the lowest aGVHD, cGVHD, and ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723016408

Risks of Patient and Donor Genetics in Allogeneic ... Patients in remission who proceeded to second allo-HSCT demonstrated >50% survival at a median follow-up of 3.7 years [7]; however, the patients who never ...

9. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101760

Early Cardiovascular Events in Recipients of Allogeneic ... Eighty-five patients died due to transplant-related causes. The cumulative incidence of nonrelapse mortality was 9.94% (95% CI: 7.98%-12.13%) at ...