Stem Cell Transplant with Conditioning Regimen for Blood Diseases

Recruiting in Palo Alto (17 mi)

Overseen by Lauri Burroughs

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: Idiopathic aplastic anemia, Fanconi anemia, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II clinical trial studies how well treosulfan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin (rATG) before donor stem cell transplantation works in treating patients with nonmalignant (non-cancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (non-cancerous) diseases such as primary immunodeficiency disorders, immune dysregulatory disorders, hemophagocytic lymphohistiocytosis, bone marrow failure syndromes, and hemoglobinopathies. Powerful chemotherapy drugs are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan, thiotepa, and fludarabine phosphate) results in new blood-forming cells (engraftment) of the new donor cells without increased toxicities in patients with nonmalignant (non-cancerous) diseases.

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 Stem Cell Transplant with Conditioning Regimen for Blood Diseases?

Research shows that using a combination of drugs like fludarabine, thiotepa, and antithymocyte globulin in conditioning regimens for stem cell transplants can lead to successful engraftment (when the donor cells start to grow and make healthy blood cells) and improved survival rates in patients with severe blood diseases, while reducing treatment-related complications. ^{1 2 3 4 5}

Is the stem cell transplant with conditioning regimen generally safe for humans?

The stem cell transplant with conditioning regimens using drugs like fludarabine, thiotepa, and treosulfan has been generally well tolerated in various studies, with some patients experiencing complications such as graft-versus-host disease (GVHD) and regimen-related toxicity. However, reduced-toxicity regimens have shown improved survival rates, indicating that these treatments can be safe for many patients, though risks remain. ^{1 2 3 6 7}

How is the stem cell transplant treatment with fludarabine, rabbit anti-thymocyte globulin, thiotepa, and treosulfan different from other treatments for blood diseases?

This treatment is unique because it combines multiple drugs to prepare the body for a stem cell transplant, aiming to reduce the risk of complications like graft-versus-host disease (when the new immune cells attack the body) and improve the chances of successful engraftment (when the new stem cells start to grow and make healthy blood cells). It uses a combination of drugs that are less intense than traditional regimens, which may be better tolerated by patients who are not strong enough for more aggressive treatments. ^{1 2 3 8 9}

Research Team

Lauri Burroughs

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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 cannot have a bone marrow or stem cell collection procedure.

Trial Timeline

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

Treatment Details

Interventions

• Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
• Fludarabine Phosphate (Anti-metabolites)
• Rabbit Anti-Thymocyte Globulin (Immunosuppressant)
• Thiotepa (Alkylating agents)
• Treosulfan (Alkylating agents)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Fred Hutch/University of Washington Cancer Consortium Seattle, WA

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Patients Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Patients Recruited

1,341,000+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Thiotepa and fludarabine (TT-FLUDA) as conditioning regimen in poor candidates for conventional allogeneic hemopoietic stem cell transplant. [2019]

3. United States 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. [2018]

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

Treosulfan-based conditioning and hematopoietic cell transplantation for nonmalignant diseases: a prospective multicenter trial. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. [2013]

6. England 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. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. [2013]

8. United States 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. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Thiotepa and antithymocyte globulin-based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high-risk hematological malignancies. [2023]