Stem Cell Transplant for Blood Disorders

Overseen By Lisa Burke

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Active infection, Pregnant, HIV positive, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of different stem cell transplant methods for individuals with non-cancerous blood disorders, such as Sickle Cell Disease, Thalassemia, and Diamond Blackfan Anemia. It evaluates three approaches to preparing patients for the transplant process. The Myeloablative Preparative Regimen (or High-Dose Chemotherapy) is designed for those with a sibling donor. The Reduced Intensity Preparative Regimen suits patients with mild iron exposure, while the Reduced Toxicity Ablative Regimen targets those with significant iron exposure. Suitable candidates have one of these blood disorders and an identified stem cell donor. As an unphased trial, this study provides a unique opportunity to explore innovative transplant methods for non-cancerous 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that different preparation methods for stem cell transplants vary in safety levels.

For the Myeloablative Preparative Regimen, studies indicate it can be used safely. This method clears out bone marrow and weakens the immune system to help the new cells settle in. However, it is quite strong and may cause more side effects, such as low blood counts and a higher risk of infection.

The Reduced Toxicity Ablative Regimen uses drugs like busulfan and fludarabine to lower these risks. Most people experience mild issues like mouth sores, and serious problems are rare. This regimen is designed to be gentler on the body while still working effectively.

Lastly, the Reduced Intensity Preparative Regimen has been shown to be safer for some patients, especially older ones. It uses lower doses to reduce the risk of severe side effects, lowering the chance of complications after the transplant.

In summary, while all regimens carry risks, the reduced toxicity and reduced intensity options aim to lessen these risks compared to the more intense myeloablative regimen. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about stem cell transplants for blood disorders because they offer tailored approaches to treatment. The Myeloablative Preparative Regimen is intense and suitable for patients with severe thalassemia, using matched sibling donors or unrelated umbilical cord blood. In contrast, the Reduced Toxicity Ablative Regimen aims to minimize side effects for younger patients or those with mild iron exposure by using a gentler approach. Lastly, the Reduced Intensity Preparative Regimen is designed for older patients with significant iron exposure, using unrelated donor bone marrow. Unlike traditional treatments that may not address varying patient needs, these regimens provide more personalized options, potentially improving outcomes and reducing complications.

What evidence suggests that this trial's treatments could be effective for blood disorders?

Research has shown that stem cell transplants may help treat blood disorders. In this trial, participants may receive one of several preparative regimens. Studies have demonstrated that the Myeloablative Preparative Regimen works well for patients not in full remission, with survival rates of 40% and 23% at two years. The Reduced Intensity Preparative Regimen offers a lower risk of serious side effects while still controlling tumors, achieving a 67% survival rate over five years. The Reduced Toxicity Ablative Regimen, also under study, focuses on reducing side effects. Although it may not improve results beyond the reduced-intensity approach, it better manages side effects. These treatments have the potential to improve outcomes for patients with blood disorders. ^{1 3 4 6 7}

Who Is on the Research Team?

Ashish Gupta, MD, PhD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Are You a Good Fit for This Trial?

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

Pregnant or breastfeeding

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

You have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants undergo a preparative regimen, which may include myeloablative, reduced toxicity ablative, or reduced intensity regimens based on donor type and patient condition

4-6 weeks

Stem Cell Transplantation

Participants receive hematopoietic stem cell transplantation

1 day

Follow-up

Participants are monitored for safety and effectiveness after transplantation

6 months to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Myeloablative Preparative Regimen
• Reduced Intensity Preparative Regimen
• Reduced Toxicity Ablative Regimen

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union 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 United States 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 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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4102707/

Conditioning regimens for hematopoietic cell transplantation Of note, these studies showed efficacy of this regimen in patients not in complete remission but with high NRM rates, resulting in 40% and 23% 2-year survival ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11530400/

Comparing transplant outcomes in ALL patients after ... The optimal myeloablative conditioning regimen for ALL patients undergoing hematopoietic cell transplant (HCT) with an alternative donor is ...

3. haematologica.org haematologica.org/article/view/12119/78493

Intensified conditioning with high-dose total marrow These data suggest that the addition of TMI to myeloablative FluBu4 in our study enhanced the efficacy of the conditioning regimen without.

4. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/myeloablative-conditioning

Myeloablative Conditioning - an overview Myeloablative conditioning regimens for hematopoietic cell transplantation (HCT) have been an effective treatment for many patients with hematologic ...

5. jhoponline.com jhoponline.com/issue-archive/2021-issues/august-2021-vol-11-no-4/18992-myeloablative-and-reduced-intensity-preparative-regimens-for-allogeneic-transplant-in-the-outpatient-versus-inpatient-setting-in-patients-with-acute-myeloid-leukemia-or-myelodysplastic-syndromes

Myeloablative and Reduced-Intensity Preparative ... RESULTS: A total of 221 patients were included in the final analysis, including 89 patients who received their preparative chemotherapy regimen in the ...

6. astctjournal.org astctjournal.org/article/S2666-6367(22)01404-X/fulltext

High dose (conditioning) regimens used prior to ... High-dose (or conditioning) regimens are preparative chemotherapy-based regimens used before ASCT. High-dose melphalan is the most commonly used regimen in MM ...

7. ashpublications.org ashpublications.org/blood/article/104/3/865/18477/Nonablative-versus-reduced-intensity-conditioning

Nonablative versus reduced-intensity conditioning regimens ... Intensity of the preparative regimen is an important component of allogeneic transplantations for myelodysplasia (MDS) or acute myelogenous leukemia (AML).