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

154 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or unrelated donors HSCT when no matched donors are available, to treat malignant and nonmalignant disorders for which HSCT is the recommended best available therapy. Initially this device will be used in a single-center, open-label, single-arm, phase II clinical trial to evaluate the efficacy of haploidentical PBSC grafts depleted of TCRα/β+ and CD19+ cells using the CliniMACS® TCRαβ/CD19 System in children and adults with hematological and non-hematological malignancies.

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

The available research shows that Stem Cell Transplant for Blood Diseases is an effective treatment for certain blood conditions. For example, it is considered a treatment of choice for patients with leukemia and myelodysplastic syndrome, as it can eliminate the disease-causing cells. In China, significant improvements have been made in using this treatment for conditions like aplastic anemia, which is a serious blood disorder. Additionally, for severe aplastic anemia, this treatment has been shown to reduce complications like graft-versus-host disease, which is when the transplanted cells attack the patient's body. While there are risks involved, such as potential relapse and complications, the treatment can be life-prolonging for some patients with advanced blood diseases. ^{1 2 3 4 5}

What safety data is available for stem cell transplants for blood diseases?

Allogeneic hematopoietic stem cell transplantation (HSCT) is associated with significant risks, including morbidity and mortality. The primary risks include delayed immune reconstitution and graft-versus-host disease (GVHD). While the procedure offers potential cures for various diseases, it is not without complications. Early complications occur within the first 100 days, while late complications arise after 100 days post-transplant. Despite these risks, the donation process itself is generally safe, with the main risk being related to anesthesia. Serious adverse events are rare, with a low incidence of cardiac events and only one fatal event reported in a large study. Overall, while allogeneic HSCT has potential benefits, it requires careful consideration and monitoring due to its associated risks. ^{6 7 8 9 10}

Is the treatment Allogeneic Stem Cell Transplant a promising treatment for blood diseases?

Yes, Allogeneic Stem Cell Transplant is a promising treatment for blood diseases. It can potentially cure diseases by replacing diseased blood or immune systems with healthy donor cells. It has shown success in treating conditions like leukemia, myelodysplastic syndrome, aplastic anemia, and sickle cell anemia. This treatment offers a chance for a cure by eradicating the disease and providing a new, healthy system. ^{1 2 6 11 12}

Research Team

Alice Bertaina, MD, PhD

Principal Investigator

Associate Professor of Pediatrics, Stem Cell Transplantation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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.

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+

Findings from Research

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 (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]

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. Serbia 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]. [2019]

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

Allo-Hematopoietic Stem Cell Transplant in China: 2014 Update. [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Allogeneic stem cell transplantation in patients above 55: suggestion for a further stratification of the HCT-CI. [2021]

4. England 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. [2021]

5. Switzerland 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. [2014]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Scotland pubmed.ncbi.nlm.nih.gov

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. [2022]

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

Safety of bone marrow stem cell donation: a review. [2010]

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

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

10. North Macedonia pubmed.ncbi.nlm.nih.gov

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report. [2020]

11. Turkey pubmed.ncbi.nlm.nih.gov

Frequency of Finding Family Donors: A Single Center Experience. [2018]

12. Italy pubmed.ncbi.nlm.nih.gov

Reduction of intramedullary apoptosis after stem cell transplantation in black african variant of pediatric sickle cell anemia. [2021]