Stem Cell Transplant for Leukemia

Overseen By Claudia Torralbas, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Guenther Koehne

Disqualifiers: Pregnancy, Active infection, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate whether processing blood stem cell transplants using an investigational device (the CliniMACS system) results in less complications for patients undergoing transplant for treatment of a blood malignancy (cancer) or blood disorder.

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 the treatment CD34+ Transplants for leukemia?

Research shows that higher doses of CD34+ cells in transplants from HLA-identical siblings are linked to lower treatment failure and relapse rates in leukemia patients. This suggests that CD34+ transplants can be effective in improving outcomes for leukemia patients. ^{1 2 3 4 5}

Is stem cell transplant using CD34+ cells generally safe for humans?

Stem cell transplants using CD34+ cells have been studied for various conditions, and while they can lead to complications like graft-versus-host disease (GVHD), the risk can be managed by adjusting the cell dose. Studies show that using purified CD34+ cells can reduce the incidence of GVHD and is associated with low toxicity, making it generally safe for humans. ^{6 7 8 9 10}

How does the CD34+ stem cell transplant treatment for leukemia differ from other treatments?

The CD34+ stem cell transplant treatment for leukemia is unique because it uses a high dose of specific stem cells to help overcome the body's resistance to accepting the transplant, even when there are genetic differences between the donor and recipient. This approach can potentially allow for successful transplants from donors who are not a perfect genetic match, which is a significant advancement over traditional bone marrow transplants that require closely matched donors. ^{2 11 12 13 14}

Research Team

Guenther Koehne, MD, PhD

Principal Investigator

Baptist Health South Florida/Miami Cancer Institute

Eligibility Criteria

This trial is for adults aged 18-74 with certain types of leukemia or lymphoma, such as AML not in 'good risk' remission, ALL/CLL at high relapse risk or second remission, CML unresponsive to specific drugs, and some non-Hodgkin's lymphomas. Participants need a performance status of ≥70%, no active infections or HIV/HTLV, not pregnant/breastfeeding, and must have good heart, liver, kidney and lung function.

Inclusion Criteria

I am between 18 and 74 years old.

Each patient must be willing to participate as a research subject and must sign an informed consent form

I am mostly able to care for myself but cannot do any heavy physical work.

Exclusion Criteria

Patient seropositive for HIV-I /II; HTLV -I /II

My leukemia has spread to my brain.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a blood stem cell transplant using the CliniMACS system, with conditioning regimens including TBI/Thiotepa/Cyclophosphamide or Busulfan/Melphalan/Fludarabine

1-2 weeks

Follow-up

Participants are monitored for disease-free survival, incidence of GvHD, and transplant-related mortality

Two years

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

Two years

Treatment Details

Interventions

• CD34+ Transplants

Trial Overview The study tests if using the CliniMACS system to process blood stem cell transplants can reduce complications in patients with blood cancers/disorders. It involves conditioning treatments like TBI (Total Body Irradiation), Thiotepa, Cyclophosphamide among others before transplanting CD34+ selected cells.

Participant Groups

Group I: Regimen B: Busulfan/Melphalan/Fludarabine Experimental Treatment 3 Interventions

Patients in enrolled in Regimen B will receive the following: * Busulfan, IV 0.8 mg/kg q6hours x 10 or 12 doses over 3 days, depending on the disease * Melphalan, 70 mg/m\^2/day x 2 days via IV infusion over 30 minutes daily * Fludarabine, 25 mg/m\^2/day x 5 days via IV infusion over 30 minutes daily

Group II: Regimen A: TBI/Thiotepa/Cyclophosphamide Experimental Treatment 3 Interventions

Patients in enrolled in Regimen A will receive the following: * Total Body Irradiation (TBI), hyper-fractionated to a dose of 1320 cGy depending on age, stage of disease and requirement of general anesthesia with lung shielding * Thiotepa, 5 mg/kg/day x 2 days via IV infusion over 4 hours daily or 10 mg/kg on one day * Cyclophosphamide, 60 mg/kg/day x 2 days via IV infusion over 2 hours daily (or if cyclophosphamide is contraindicated, fludarabine at 25 mg/m\^2 x 5 days may be substituted)

Who Is Running the Clinical Trial?

Guenther Koehne

Lead Sponsor

Trials

4

Recruited

160+

Baptist Health South Florida

Lead Sponsor

Trials

54

Recruited

8,100+

Findings from Research

A study of 506 adult patients receiving CD34+ selected hematopoietic stem cell transplants showed that using a combined prognostic model of Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) can effectively predict overall survival and relapse-free survival outcomes.

Patients with a high DRI had a significantly increased risk of death and relapse compared to those with low/intermediate DRI, indicating that this model can help in selecting the best candidates for CD34+ selected transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. Cho, C., Hilden, P., Avecilla, ST., et al.[2022]

A higher dose of CD34+ cells (> 8.5 × 10^6/kg) during allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with improved progression-free survival (PFS), with a significant odds ratio of 0.36, indicating a lower risk of disease progression.

While higher CD34+ cell doses may enhance PFS, they also raise concerns about potential complications, such as graft-versus-host disease (GVHD), highlighting the need for careful consideration of cell dosing in transplantation protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of CD34+ Cell Dose with Progression-free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation in Children with Hematologic Malignancies. Wang, YL., Chang, TY., Hsieh, HY., et al.[2023]

HLA mismatched hemopoietic stem cell transplants can be successfully performed, as all seven patients in the study achieved engraftment and complete remission after receiving the transplants.

The conditioning regimen of busulfan and cyclophosphamide, with the addition of antithymocyte globulin, was effective, and G-CSF mobilized peripheral blood stem cells proved to be a viable source for these transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia]. Huang, X., Chen, Y., Han, W., et al.[2018]

References

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

Hematopoietic cell transplantation in the treatment of leukemia. [2019]

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

Bone marrow transplantation: current results in leukemia. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[The impact of CD34(+) cells and T cells subsets in grafts on prognosis of HLA-identical sibling allogeneic peripheral blood stem cell transplantation]. [2009]

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

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation. [2022]

5. 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]

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

Association of CD34+ Cell Dose with Progression-free Survival after Allogeneic Peripheral Blood Hematopoietic Cell Transplantation in Children with Hematologic Malignancies. [2023]

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

The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors. [2021]

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

Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemia. [2021]

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

Transplantation of highly purified peripheral-blood CD34+ progenitor cells from related and unrelated donors in children with nonmalignant diseases. [2006]

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

Transplant dose of CD34(+) and CD3(+) cells predicts outcome in patients with haematological malignancies undergoing T cell-depleted peripheral blood stem cell transplants with delayed donor lymphocyte add-back. [2019]

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

Tolerance induction by "megadose" hematopoietic transplants: donor-type human CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T lymphocyte precursors in mixed lymphocyte culture. [2019]

12. Germany pubmed.ncbi.nlm.nih.gov

Stem cell transplantation. [2013]

13. Japan pubmed.ncbi.nlm.nih.gov

Marrow transplantation: the Seattle experience. [2008]

14. China pubmed.ncbi.nlm.nih.gov

[Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia]. [2018]