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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a special stem cell selection method, known as CD34 Stem Cell Selection Therapy, to assist individuals with bone marrow failure syndromes. The focus is on reducing complications like graft versus host disease, which can occur after a stem cell transplant. Researchers aim to evaluate how well this method improves survival and reduces infections in patients receiving donor stem cells. Individuals with a non-cancerous condition affecting their bone marrow who require a second stem cell transplant might be suitable candidates for this study. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in stem cell therapy.

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 prior data suggests that CD34 Stem Cell Selection Therapy is safe?

Research has shown that CD34+ Stem Cell Selection Therapy is generally safe. Studies have found that patients with various conditions tolerate it well. The data indicate that side effects are usually mild and manageable. For instance, using CD34-selected stem cells has improved patients' conditions without causing serious harm.

This therapy aims to lower the risk of graft versus host disease (GVHD), a common transplant issue where donor cells attack the patient's body. By reducing this risk, CD34+ Stem Cell Selection Therapy helps make stem cell transplants safer and more effective. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bone marrow failure?

Researchers are excited about CD34 Stem Cell Selection Therapy for bone marrow failure syndromes because it offers a novel approach to reducing complications associated with bone marrow transplants. Unlike traditional treatments that usually rely on unmodified donor cells, this therapy uses the CliniMACS PLUS system to select CD34+ stem cells and remove T-cells, significantly decreasing the risk of graft versus host disease (GVHD). This targeted cell selection could lead to a safer transplant process, potentially improving patient outcomes and expanding treatment options for those with pre-transplant complications.

What evidence suggests that CD34 Stem Cell Selection Therapy might be an effective treatment for bone marrow failure syndromes?

Research has shown that CD34 Stem Cell Selection Therapy could help treat bone marrow failure syndromes. One study found that 72% of patients fully recovered their blood health, and 80% showed overall improvement. After about three and a half years, more than half of the patients remained alive. This therapy is considered safe and effective, especially for those struggling to produce blood cells after a previous stem cell transplant. It aims to lower the risk of graft versus host disease, where the transplanted cells attack the body. Overall, CD34 Stem Cell Selection Therapy shows promising results for patients with serious blood disorders.

In this trial, participants will receive CD34 Stem Cell Selection Therapy using the CliniMACS PLUS system, followed by a chemotherapy regimen. This approach is designed to enhance treatment outcomes and reduce complications such as graft versus host disease. ^{3 4 5 6 7}

Who Is on the Research Team?

Diane George, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

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

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

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721010770

Outcomes with CD34-Selected Stem Cell Boost for Poor ... Complete and overall hematologic response rates were 72% and 80%, respectively. After a median follow-up of 42 months, the actuarial survival rate was 54%.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9825630/

Durable engraftment and excellent overall survival after ... Historically, outcomes of patients with PGF have been very poor, and there are no standardized approaches to treatment. Furthermore, few outcomes after CD34- ...

3. withpower.com withpower.com/trial/phase-2-anemia-sickle-cell-2-2013-fc868

CD34+ Stem Cell Selection for Bone Marrow Failure ... In a study involving 32 patients, CD34+ cell selection for transplantation showed comparable hematopoietic recovery to unmanipulated peripheral blood stem and ...

4. ashpublications.org ashpublications.org/bloodadvances/article/8/17/4729/516114/Active-infection-at-the-time-of-CD34-selected-stem

Active infection at the time of CD34+ selected stem cell boost ... CD34 selected SCB is a safe and effective treatment for patients with post–allo-HCT cytopenias, with most published data in the context of PGF.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01966367?term=diamond+blackfan+anemia

CD34+ (Non-Malignant) Stem Cell Selection for Patients ... This study's goal is to determine the frequency and severity of acute graft versus host disease, to evaluate incidence of primary and secondary graft ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03626285

Bone Marrow Transplantation Using CD34-Selected Stem ... This expanded access protocol studies bone marrow transplantation using CD34-selected stem cells from related or unrelated donors in treating participants with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8432362/

Allogeneic Stem Cell Transplantation with CD34+ ... In this review, we summarize the main characteristics of allogeneic stem cell transplant with CD34+ cell selection including risks of graft failure, GvHD, ...