Stem Cell Transplant for Blood Disorders

Overseen By Lisa Burke

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Masonic Cancer Center, University of Minnesota

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is studying how well stem cell transplants work for patients with blood diseases that are not cancer. The treatment involves giving patients healthy stem cells from a donor to replace their damaged or diseased cells. This method is the oldest and most widely used technique of stem cell transplant, primarily used to treat blood disorders.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What data supports the idea that Stem Cell Transplant for Blood Disorders is an effective treatment?

The available research shows that using reduced-intensity or nonmyeloablative regimens for stem cell transplants can be effective for treating blood disorders. These approaches are less toxic and still allow the treatment to work by helping the body fight the disease. For example, one study found that using a specific regimen called FluBU resulted in good survival rates, with 80% of standard-risk patients surviving and 70% not experiencing any major issues after treatment. This suggests that stem cell transplants can be as effective as other more intense treatments but with fewer side effects. ^{1 2 3 4 5}

What safety data exists for stem cell transplants for blood disorders?

Safety data for stem cell transplants, including various conditioning regimens, indicate that nonmyeloablative and reduced-toxicity regimens generally reduce treatment-related morbidity compared to traditional myeloablative regimens. These regimens are associated with lower mucosal toxicities and myelopoiesis effects, while still allowing for effective engraftment and graft-vs-malignancy effects. Studies show that reduced-toxicity regimens, such as those using busulfan and fludarabine, have promising safety profiles with lower rates of acute and chronic graft-versus-host disease (GVHD) and treatment-related mortality (TRM). However, larger studies are needed to further compare their safety and efficacy to traditional regimens. ^{1 2 4 6 7}

Is the treatment 'Myeloablative Preparative Regimen, Reduced Intensity Preparative Regimen, Reduced Toxicity Ablative Regimen' promising for blood disorders?

Yes, this treatment is promising because it reduces the risk of complications and treatment-related deaths compared to traditional methods. It allows older patients and those with other health issues to receive treatment, and it still effectively fights blood disorders by using the body's immune response to target disease. ^{1 2 3 8 9}

Research Team

Ashish Gupta, MD, PhD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for people with serious blood disorders like Sickle Cell Disease and Thalassemia, who have a suitable stem cell donor. They must be in stable heart health, have reasonable physical function, and normal liver/kidney function. It's not for those with active infections, pregnant or breastfeeding women, or HIV-positive individuals.

Inclusion Criteria

My heart functions well, without severe failure or uncontrolled irregular heartbeat.

Your bilirubin, aspartate aminotransferase, and alkaline phosphatase levels are not more than 5 times the normal limit at the hospital where you are being treated.

I have a suitable stem cell donor or source.

Exclusion Criteria

I currently have an infection that isn't under control.

Pregnant or breastfeeding

You have HIV.

Treatment Details

Interventions

• Myeloablative Preparative Regimen (Chemotherapy)
• Reduced Intensity Preparative Regimen (Chemotherapy)
• Reduced Toxicity Ablative Regimen (Chemotherapy)

Trial Overview The study tests different ways to prepare patients for stem cell transplants using less intense chemotherapy (reduced intensity/toxicity regimens) or stronger chemo (myeloablative regimen), aiming to treat non-cancerous blood diseases.

Participant Groups

Group I: Reduced Toxicity Ablative Regimen Experimental Treatment 1 Intervention

For use in patients with a matched sibling donor or unrelated UCB donor and DBA patients who are \<12 years and/or have mild/moderate iron exposure.

Group II: Reduced Intensity Preparative Regimen Experimental Treatment 1 Intervention

For use in patients with unrelated donor bone marrow and for DBA patients who are \>12 years and/or have significant iron exposure.

Group III: Myeloablative Preparative Regimen Experimental Treatment 1 Intervention

For use in patients with a matched sibling donor, unrelated umbilical cord blood and in those with severe thalassemia.

Myeloablative Preparative Regimen is already approved in Canada, Japan for the following indications:

Approved in Canada as Myeloablative Conditioning Regimen for:

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)
• Acute Lymphoblastic Leukemia (ALL)
• Chronic Myeloid Leukemia (CML)
• High-Risk Hemoglobinopathies

Approved in Japan as Myeloablative Conditioning Regimen for:

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)
• Acute Lymphoblastic Leukemia (ALL)
• Chronic Myeloid Leukemia (CML)
• High-Risk Hemoglobinopathies

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

Nonmyeloablative or reduced-intensity preparative regimens for allogeneic hematopoietic transplantation can effectively treat hematologic malignancies while significantly lowering the risk of complications compared to high-dose myeloablative therapy.

These regimens utilize either immunosuppressive chemotherapeutic drugs or low-dose total body irradiation, allowing for engraftment and beneficial graft-vs-malignancy effects, making them potentially curative for certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation. Biology and current indications. Champlin, R., Khouri, I., Anderlini, P., et al.[2005]

Nonmyeloablative conditioning regimens for allogeneic stem cell transplantation may reduce the risk of bacterial infections linked to mucosal damage and prolonged neutropenia, compared to traditional myeloablative regimens.

Despite the benefits, patients undergoing nonmyeloablative transplantation still face risks of late viral and fungal infections, especially during severe graft versus host disease, indicating a need for ongoing research into infection prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious risks and outcomes after stem cell transplantation: are nonmyeloablative transplants changing the picture? Junghanss, C., Marr, KA.[2021]

In a study of 100 patients with hematological malignancies undergoing allogeneic stem cell transplantation using a reduced-intensity conditioning regimen, the 5-year overall survival rate was 60%, indicating a promising long-term outcome for this treatment approach.

The study found that 71% of patients with measurable disease achieved a response, and nonrelapse mortality was significantly associated with acute graft-vs.-host disease, highlighting the importance of managing this complication for better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning with Fludarabin, oral Busulfan, and thymoglobulin allows long-term disease control and low transplant-related mortality in patients with hematological malignancies. Blaise, D., Farnault, L., Faucher, C., et al.[2016]

The FluBU conditioning regimen, used in a study of 36 adult patients with myeloid or lymphoid malignancies, demonstrated a manageable safety profile with limited toxicity, showing acute graft-versus-host disease (GVHD) in 19% of patients and chronic GVHD in 37%.

Overall survival rates were significantly different between standard-risk (80%) and high-risk (35%) patients, indicating that while FluBU is effective, its efficacy varies based on the patient's risk level for relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? Chunduri, S., Dobogai, LC., Peace, D., et al.[2013]

In a study of 29 adults undergoing allogeneic stem-cell transplantation, a higher dose of thiotepa (10 mg/kg) resulted in significantly better overall survival (87% vs. 46%) and progression-free survival (87% vs. 30%) compared to a lower dose (5 mg/kg) after one year.

The study found that the lower dose (5 mg/kg) was associated with a higher transplant-related mortality (14% at one year), indicating that patients who are fit for the higher dose should be prioritized for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation. El-Cheikh, J., Massoud, R., Moukalled, N., et al.[2019]

A reduced-toxicity myeloablative conditioning regimen using dose-adjusted busulfan, fludarabine, antithymocyte globulin, and total body irradiation was evaluated in 40 pediatric patients with high-risk leukemias, showing overall survival rates of 67% at two years and 51% at five years post-transplant.

The regimen demonstrated safety with a transplant-related mortality of 8% at 100 days and 13% at one year, and it was particularly effective for patients with myeloid disease who achieved a busulfan exposure above 4000 μmol*min/day, leading to a two-year relapse-free survival rate nearing 80%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-toxicity conditioning regimen with busulfan, fludarabine, rATG, and 400 cGy TBI in pediatric patients undergoing hematopoietic stem cell transplant for high-risk hematologic malignancies. Rossoff, J., Jacobsohn, D., Kwon, S., et al.[2022]

In a study of 130 patients with hematologic malignancies, a reduced intensity regimen before allogeneic transplantation achieved a high engraftment rate of 94%, indicating its efficacy in facilitating stem cell engraftment.

Factors such as having an HLA identical sibling donor and achieving complete remission were associated with significantly better event-free survival and lower relapse rates, highlighting the importance of donor matching and disease status in transplantation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation. Belkacémi, Y., Labopin, M., Hennequin, C., et al.[2007]

The use of nonmyeloablative conditioning, such as fludarabine and 2 Gy TBI, has reduced the toxicity of allogeneic stem cell transplantation, making it safer for older patients and those with other health issues.

This approach has shown promise in treating aggressive non-Hodgkin's lymphoma and mantle cell NHL by allowing effective allogeneic engraftment while minimizing the risks associated with traditional myeloablative conditioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation following nonmyeloablative conditioning for aggressive lymphoma. Maloney, D.[2008]

Reduced-intensity and nonmyeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) allow for effective treatment of older patients and those with comorbid conditions, minimizing toxicity compared to traditional myeloablative regimens.

These regimens successfully prevent host-versus-graft rejection and promote anti-tumor effects, making them a promising option for patients with hematologic malignancies or inherited blood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning as treatment for hematologic malignancies and inherited blood disorders. Baron, F., Storb, R.[2021]

References

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

Nonmyeloablative preparative regimens for allogeneic hematopoietic transplantation. Biology and current indications. [2005]

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

Infectious risks and outcomes after stem cell transplantation: are nonmyeloablative transplants changing the picture? [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning with Fludarabin, oral Busulfan, and thymoglobulin allows long-term disease control and low transplant-related mortality in patients with hematological malignancies. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? [2013]

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

Thiotepa 10 mg/kg Treatment Regimen Is Superior to Thiotepa 5 mg/kg in TBF Conditioning in Patients Undergoing Allogeneic Stem-Cell Transplantation. [2019]

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

Reduced-toxicity conditioning regimen with busulfan, fludarabine, rATG, and 400 cGy TBI in pediatric patients undergoing hematopoietic stem cell transplant for high-risk hematologic malignancies. [2022]

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

Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation. [2007]

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

Allogeneic transplantation following nonmyeloablative conditioning for aggressive lymphoma. [2008]

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

Allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning as treatment for hematologic malignancies and inherited blood disorders. [2021]