CD34+ Stem Cell Selection for Bone Marrow Failure Syndromes

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Diane George

Disqualifiers: Uncontrolled infection, Pregnancy, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

37 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a special machine to filter out harmful cells from donor blood to make stem cell transplants safer for young patients with non-cancerous diseases. By removing specific cells, it aims to prevent a serious immune reaction.

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 CD34 Stem Cell Selection Therapy for bone marrow failure syndromes?

Research shows that CD34+ stem cell selection can help reduce complications like graft-versus-host disease (a condition where the donor cells attack the recipient's body) and support successful blood cell recovery in patients undergoing stem cell transplants. This suggests it may be beneficial for treating bone marrow failure syndromes. ^{1 2 3 4 5}

Is CD34+ Stem Cell Selection Therapy safe for humans?

CD34+ Stem Cell Selection Therapy has been shown to be safe and well-tolerated in patients with various cancers, with no adverse reactions observed during studies. It is associated with good recovery of blood cell counts and is considered a safe procedure in transplantation medicine. ^{5 6 7 8 9}

How does CD34 Stem Cell Selection Therapy differ from other treatments for bone marrow failure syndromes?

CD34 Stem Cell Selection Therapy is unique because it involves selecting and transplanting only CD34+ stem cells, which are known for their ability to regenerate blood cells, potentially reducing the risk of complications from unwanted cells like T-cells or tumor cells. This method aims to improve the purity and effectiveness of the transplant, which is not typically achieved with standard bone marrow transplants. ^{1 3 4 5 10}

Research Team

Diane George, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for children, adolescents, and young adults with various non-malignant diseases like sickle cell anemia or immune deficiencies. Participants must be under 40 years old, have a matched family or unrelated adult donor for stem cells, and good organ function. Pregnant women and those with uncontrolled infections or certain complications from sickle cell anemia are excluded.

Inclusion Criteria

Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol and must sign an informed consent in accordance with institutional policies approved by the U.S. Department of Health and Human Services.

You have certain blood disorders as outlined in the study's guidelines.

I am 40 years old or younger. If I have sickle cell anemia, I am at least 2 years old.

Exclusion Criteria

I have sickle cell anemia but no recent severe infections, HIV, or recent HCT.

I do not have any untreated infections.

Pregnancy/Breast-Feeding: Females who are pregnant or breast feeding at the time of study entry are not eligible.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Participants receive a pre-transplant conditioning regimen of Busulfan, Fludarabine, and Alemtuzumab, or Melphalan for those with hepatic dysfunction

2-3 weeks

Stem Cell Transplantation

Participants undergo CD34+ stem cell selection and transplantation to decrease the risk of acute and chronic GVHD

1 week

Post-transplant Monitoring

Participants are monitored for engraftment, GVHD, and infectious complications

100 days

Follow-up

Participants are monitored for long-term outcomes including survival and immune reconstitution

5 years

Treatment Details

Interventions

• CD34 Stem Cell Selection Therapy

Trial Overview The study tests CD34 Stem Cell Selection Therapy in patients receiving allogeneic peripheral blood stem cell transplants. It aims to assess the treatment's impact on graft versus host disease, graft rejection, survival rates, immune system recovery timeframes, and infection incidences post-transplant.

Participant Groups

Group I: CliniMACS PLUS followed by chemotherapy Experimental Treatment 1 Intervention

Patients will receive a pre-transplant conditioning regimen of Busulfan Fludarabine and Alemtuzumab. For patients with pre-transplant hepatic dysfunction, Melphalan will be substituted for the Busulfan. For patients receiving a second transplant or a "boost", pre-transplant conditioning based on the clinical condition of the patient will be determined by the Principal Investigator and the patient's bone marrow transplantation (BMT) physician. The donor peripheral blood stem cells will undergo CD34+ selection (Biological/Vaccine: CD34 Stem Cell Selection Therapy). The CliniMACS (PLUS) Reagent System will be used to remove T-cells from the peripheral blood stem cell transplant in order to decrease the risk of acute and chronic graft versus host disease (GVHD).

Who Is Running the Clinical Trial?

Diane George

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

In a study involving 11 transplant recipients, it was found that those who received CD34(+)-selected transplants had a similar frequency of Lin(-)CD34(-) precursor cells compared to normal donors and recipients of other transplant types, suggesting no immediate difference in cell population.

However, the Lin(-)CD34(-) cells from CD34-enriched transplant recipients did not develop into CD34(+) cells or show colony-forming activity after 7 days in culture, indicating a potential defect in their ability to differentiate, which may have long-term clinical implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of a CD34- hematopoietic precursor population in recipients of CD34+ stem cell transplantation. Kato, S., Ando, K., Nakamura, Y., et al.[2006]

In a study involving 32 patients, CD34+ cell selection for transplantation showed comparable hematopoietic recovery to unmanipulated peripheral blood stem and progenitor cells (PBPCs), despite a lower efficiency in collecting certain cell types like burst-forming units-erythroid (BFU-E).

A critical dose of 5 x 10(6) CD34+ cells or 40 x 10(4) colony-forming units-granulocyte-macrophage (CFU-GM) per kg is necessary for ensuring rapid recovery of neutrophils and overall hematopoietic function post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells. Beguin, Y., Baudoux, E., Sautois, B., et al.[2019]

In a study of 53 procedures involving 47 patients with hematologic malignancies and solid tumors, higher initial percentages of CD34+ cells in the starting population led to better purity and enrichment of these progenitor cells in the final product, while also reducing unwanted CD3+ and CD19+ cells.

The reinfusion of selected CD34+ cells was found to be safe and well-tolerated, with no adverse reactions reported, indicating that autologous transplantation using this method is a viable option for patients undergoing myeloablative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive selection of CD34+ cells by immunoadsorption: factors affecting the final yield and hematopoietic recovery in patients with hematological malignancies and solid tumors. Bruno, A., Caravita, T., Adorno, G., et al.[2019]

References

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

Absence of a CD34- hematopoietic precursor population in recipients of CD34+ stem cell transplantation. [2006]

2. England pubmed.ncbi.nlm.nih.gov

Allogeneic Stem Cell Transplantation with CD34+ Cell Selection. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Second transplantation with CD34+ bone marrow cells selected from a two-loci HLA-mismatched sibling for a patient with chronic myeloid leukaemia. [2019]

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

Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[Autologous transplantation of hematopoietic precursor cells following CD34 selection]. [2006]

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

Positive selection of CD34+ cells by immunoadsorption: factors affecting the final yield and hematopoietic recovery in patients with hematological malignancies and solid tumors. [2019]

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

Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses. [2019]

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

A high CD34+ cell dose is associated with better disease-free survival in patients with low-risk diseases undergoing peripheral blood stem cell transplantation from HLA-matched related donors. [2021]

9. Italy pubmed.ncbi.nlm.nih.gov

Long-term immune recovery after CD34+ immunoselected and unselected peripheral blood progenitor cell transplantation: a case-control study. [2006]

10. England pubmed.ncbi.nlm.nih.gov

The CD34 antigen: potential clinical advantages of CD34 selection. [2019]