Stem Cell Transplant for Blood Diseases

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Alice Bertaina

Disqualifiers: Pregnancy, Severe GvHD, Liver dysfunction, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

204 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to make stem cell transplants safer and more effective for individuals with blood diseases, whether cancerous or not. The focus is on using donor stem cells specially prepared to reduce risks like rejection or complications, a process known as Allogeneic Stem Cell Transplant. This approach suits those with life-threatening blood conditions, such as certain types of leukemia or blood disorders, who cannot find a fully matched donor. Researchers will monitor participants for two years to assess transplant success and any side effects. As an unphased trial, this study allows patients to contribute to groundbreaking research that could enhance future transplant safety and effectiveness.

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

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 are safe for use in stem cell transplants?

Studies have shown that stem cell transplants from donors can be safe and effective. One review found a high survival rate of 94% in certain cases. However, risks such as infections or organ problems, including heart issues, can occur.

Research on the CliniMACS TCRαβ/CD19 system, used to prepare stem cells for transplant, suggests it can lower the risk of graft-versus-host disease (GVHD). GVHD occurs when new cells attack the body, so reducing this risk is crucial for safety. Reports show low rates of both short-term and long-term GVHD with this system.

Overall, while possible side effects exist, research suggests this treatment approach is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the allogeneic stem cell transplant for blood diseases because it uses donor cells that have been manipulated through an investigational device, possibly enhancing their effectiveness in treating both malignant and non-malignant conditions. This approach is different from standard treatments like chemotherapy or radiation, which can be harsh and less targeted. The use of manipulated donor cells offers the potential for a more personalized and precise treatment, potentially improving patient outcomes while reducing side effects. Additionally, there is a compassionate arm, allowing patients who don't qualify for the experimental treatments to still benefit, broadening the scope of impact.

What evidence suggests that the CliniMACS TCR α/β Reagent Kit and CliniMACS CD19 could be effective for stem cell transplants in blood diseases?

Research has shown that stem cell transplants from donors (allogeneic transplants) can treat both cancerous and non-cancerous blood diseases. In this trial, participants with malignancies will undergo a stem cell transplant using donor cells manipulated through an investigational device, as part of the "Stem Cell Transplant - Malignant" arm. Studies indicate that these transplants can be a safe and effective option, even for patients unresponsive to other treatments, potentially leading to remission and longer survival.

For non-cancer conditions, participants in the "Stem Cell Transplant - Non-Malignant" arm will also receive donor cell transplants. Evidence suggests that allogeneic stem cell transplants often result in longer periods without disease compared to standard treatments, particularly for serious conditions like aplastic anemia, where other treatments may not work as well. Overall, these transplants have shown significant benefits in improving outcomes for various blood-related diseases. ^{6 7 8 9 10}

Who Is on the Research Team?

David Shyr, MD

Principal Investigator

Clinical Associate Professor, Pediatrics, Stem Cell Transplantation

Are You a Good Fit for This Trial?

This trial is for children and young adults under 60 with life-threatening blood diseases, who need a stem cell transplant but don't have a fully matched donor. They must be able to use birth control and have a partial genetic match with the donor. People can't join if they're pregnant, breastfeeding, have severe organ dysfunction or uncontrolled diseases.

Inclusion Criteria

I can do most activities but need help with some.

My donor and I match in at least one gene at four specific genetic locations.

I have a serious blood disorder that may improve with a stem cell transplant.

Exclusion Criteria

Any severe concurrent disease which, in the judgement of the sponsor-investigator, would place the patient at increased risk during participation in the study.

I do not have any active infections, including HIV.

I have severe graft-versus-host disease from a past transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a stem cell transplant using donor cells manipulated through an investigational device

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Stem Cell Transplant
• CliniMACS TCR α/β Reagent Kit and CliniMACS CD19

Trial Overview The study tests a new method using CliniMACS TCR α/β Reagent Kit and CD19 to remove certain cells from donor stem cells before transplanting them into patients without fully matched donors. It aims to make transplants safer and more effective for treating various malignant and non-malignant disorders.

How Is the Trial Designed?

Group I: Stem Cell Transplant -Malignant Experimental Treatment 2 Interventions

The participant with a malignancy will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.

Group II: Stem Cell Transplant - Non-Malignant Experimental Treatment 2 Interventions

The participant with a non-malignant disease will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. Participants will be followed for outcomes for two years.

Group III: Stem Cell Transplant - Compassionate Experimental Treatment 2 Interventions

Patients with malignant or non-malignant disorders who do not qualify for experimental arms but who may still benefit from participation in this study may be enrolled in this arm.

Allogeneic Stem Cell Transplant is already approved in United States, European Union for the following indications:

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

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Approved in European Union as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Who Is Running the Clinical Trial?

Alice Bertaina

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critical treatment option for various diseases, but it carries risks of morbidity and mortality, highlighting the importance of donor safety during the stem cell donation process.

Bone marrow donation is a well-established and generally safe procedure, with a low incidence of serious adverse events (only 1 fatal event reported among 27,770 donations), and the most common side effects being pain and fatigue, indicating that careful donor selection is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bone marrow stem cell donation: a review. Bosi, A., Bartolozzi, B.[2010]

The study estimates the annual need for allogeneic stem cell transplantation (SCT) in Vojvodina, indicating a total of 786 days required for related donor transplants and 306 days for unrelated donor transplants for patients with various hematological diseases.

This model can help in planning regional bone marrow donor registries and can be adapted for other diseases treatable by hematopoietic stem cell transplantation (HSCT), highlighting its potential for improving patient care and resource allocation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[General calculating model of the needs for allogenic stem cell transplantation for the patients with leukaemia and myelodysplastic syndrome in Vojvodina]. Vojvodić, S., Popović, S.[2019]

Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially replace a diseased immune system with healthy donor cells, showing promise in treating conditions like severe aplastic anemia and autoimmune diseases, but results can vary widely with both complete remissions and treatment failures reported.

Despite its potential benefits, allogeneic HSCT is associated with significant risks, including morbidity and mortality, leading to the conclusion that it cannot be generally recommended without further carefully conducted studies to identify the best patient populations and treatment technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. Gratwohl, A.[2009]

Allogeneic hematopoietic stem cell transplantation (HSCT) has the potential to cure severe autoimmune diseases by replacing a diseased immune system with a healthy one, although it carries higher risks compared to autologous HSCT, including complications and mortality.

Despite the risks, allogeneic HSCT may lead to sustained remissions in selected cases, as evidenced by outcomes in conditions like aplastic anemia and chronic myelogenous leukemia, and initial experiences in patients with systemic sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. Nash, RA.[2007]

In a study of 401 patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for advanced hematological diseases, the 5-year overall survival (OS) rate was 27.3% and disease-free survival (DFS) was 21.1%.

The analysis revealed that the type of underlying malignancy significantly affected both OS and DFS, while the development of severe acute graft versus host disease (GvHD) negatively impacted OS; interestingly, chronic GvHD was associated with better outcomes, highlighting the importance of immunological responses in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic graft versus host disease but not the intensity of conditioning has impact on survival after allogeneic hematopoietic stem cell transplantation for advanced hematological diseases. Hilgendorf, I., Wolff, D., Nogai, A., et al.[2014]

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) with sibling donors experience a complex mix of emotions, feeling both secure in their donor's support and burdened by a sense of responsibility for the donor's safety.

The study highlights the need for healthcare providers to understand the emotional challenges faced by patients and their sibling donors, as this can impact their care and overall experience during the transplantation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. Kisch, A., Bolmsjö, I., Lenhoff, S., et al.[2022]

In a study of 412 adult patients needing allogeneic hematopoietic stem cell transplants, 55% were able to find matched family donors, highlighting the importance of family screening in donor compatibility.

Among the patients who received transplants, 83% had HLA-matched related donors, emphasizing that while unrelated donor options are increasing, finding a compatible family member remains crucial for successful transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of Finding Family Donors: A Single Center Experience. Kasar, M., Yeral, M., Solmaz, S., et al.[2018]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a powerful curative option for patients with specific blood disorders, showing significant advancements in recent years.

Key improvements include the use of haploidentical HSCT and enhanced strategies for managing aplastic anemia, relapse, and graft versus host disease, particularly in the context of practices in China.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allo-Hematopoietic Stem Cell Transplant in China: 2014 Update. Lv, M., Huang, XJ.[2015]

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective curative treatment for various hematological and genetic diseases, but it can lead to both early and late complications.

A case study of a 49-year-old patient with acute myeloid leukemia (AML) highlighted the occurrence of acute graft versus host disease (GvHD) and late complications such as chronic GvHD, infections, cataracts, and secondary malignancies, emphasizing the need for awareness and education regarding these risks post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report. Trajkovska, I., Georgievski, B., Cevreska, L., et al.[2020]

In a study of 27 children with the Black African variant of sickle cell anemia who underwent allogeneic hematopoietic stem cell transplantation, all patients achieved sustained engraftment and remained free of sickle cell-related complications post-transplant.

The transplantation led to a normalization of erythroid populations in the bone marrow, indicating improved erythroid maturation and reduced apoptosis, which suggests a promising curative effect for sickle cell anemia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of intramedullary apoptosis after stem cell transplantation in black african variant of pediatric sickle cell anemia. Isgrò, A., Sodani, P., Marziali, M., et al.[2021]

In a study of 85 patients who underwent allogeneic stem cell transplantation (alloSCT), age over 60 years did not negatively impact the treatment outcomes, suggesting that older patients can safely receive this therapy.

The presence of chronic graft-versus-host disease (cGvHD) significantly improved prognosis, indicating that early withdrawal of immunosuppression may enhance the benefits of alloSCT, even in patients with comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation in patients above 55: suggestion for a further stratification of the HCT-CI. Späth, C., Busemann, C., Krüger, WH.[2021]

In a study involving 15 patients with severe aplastic anemia (SAA), high-dose allogeneic hematopoietic stem cell transplantation (allo-HSCT) using G-CSF mobilized peripheral blood and bone marrow stem cells from HLA-identical siblings resulted in successful bone marrow engraftment for all patients, with only one case of late rejection.

The treatment showed a promising safety profile, with no acute graft-versus-host disease (GVHD) observed and a low incidence of chronic GVHD at 6.67%, alongside a high three-year disease-free survival rate of 79.8%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia. Sun, ZM., Liu, HL., Geng, LQ., et al.[2021]

Citations

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Allogeneic hematopoietic cell transplantation: the state of ... ... transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. ... malignancies: an individual patient data ...

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Clinical outcomes of allogeneic hematopoietic stem cell ... Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell ...

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Efficacy and safety of hematopoietic stem cell... Efficacy and safety of hematopoietic stem cell transplantation for hematologic malignancies. A protocol for an overview of systematic reviews and meta- ...

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Allogeneic Stem Cell Transplantation in Participants With ... Study Design. Data were pooled from the multicohort phase 1b KEYNOTE-013 study, which included participants with various hematologic malignancies (NCT01953692; ...

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Feasibility and Efficacy of a Second Allogeneic Stem Cell ... We observed that second HSCT is a feasible and safe curative option for malignant hematologic diseases in the challenging setting of relapse or failure.

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Safety and efficacy of allogeneic hematopoietic stem cell ... Preclinical studies have suggested that immune activation from checkpoint blockade could lead to both increased immune-related toxicity and antitumor activity.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... This systematic review and meta-analysis present strong evidence for the safety and efficacy of allo-HSCT in SCD treatment, with an OS of 94% ...

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

Outcomes of Allogeneic Hematopoietic Stem Cell ... Allo-HCT offers curative potential for patients aged 70 and above with hematologic malignancies. •. Post-transplant relapse and infection remain the leading ...

9. cancer.org cancer.org/cancer/managing-cancer/treatment-types/stem-cell-transplant/transplant-side-effects.html

Stem Cell or Bone Marrow Transplant Side Effects Stem cell transplants can have side effects that happen soon after the transplant, as well as long term complications. Learn more here.

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

Early Cardiovascular Events in Recipients of Allogeneic ... Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with organ toxicities, including cardiovascular (CV) complications.