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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for preparing blood stem cell transplants (CD34+ Transplants) to determine if it reduces complications for individuals with certain blood cancers or disorders. A special device processes the transplants, and two different treatment plans are compared. Suitable candidates include those with leukemia or lymphoma unresponsive to other treatments, or other serious blood disorders treatable with a transplant. Participants must have manageable symptoms and be willing to engage in research. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in treatment.

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 the CliniMACS system is safe for blood stem cell transplants?

A previous study showed that using CD34+ cells for transplants can reduce a common complication called GvHD, where the donated cells attack the recipient's body. This suggests that the treatment might be well-tolerated. For Regimen A, research indicates that combining the drug Thiotepa with total body radiation and cyclophosphamide is safe for patients with acute lymphoblastic leukemia.

For Regimen B, studies have shown that using the drugs fludarabine and melphalan together can improve survival rates in older patients with myelodysplastic syndromes, a type of blood disorder. Additionally, busulfan, another drug in Regimen B, has been linked to good survival rates when used at certain doses.

Overall, these findings suggest that the treatments in this trial have generally been well-tolerated in past studies. However, since this is a Phase 2 trial, the researchers are still exploring the treatment's safety and effectiveness further. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for leukemia because they offer new combinations of chemotherapy drugs that might be more effective or tolerable than the current standard options, such as traditional chemotherapy regimens with drugs like cytarabine and daunorubicin. Regimen A is unique as it combines Total Body Irradiation (TBI) with Thiotepa and Cyclophosphamide, or Fludarabine if Cyclophosphamide can't be used, potentially leading to better disease control by using radiation and chemotherapy together. Regimen B offers another novel approach, using Busulfan, Melphalan, and Fludarabine, which might enhance leukemia cell eradication with a different drug synergy. These combinations aim to improve patient outcomes by targeting the cancer cells more effectively, possibly leading to higher remission rates and fewer side effects compared to existing treatments.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that CD34+ cell transplants can effectively treat blood cancers and disorders. In this trial, participants will receive CD34+ transplants as part of different treatment regimens. Studies suggest that using higher amounts of CD34+ cells may lead to better patient outcomes. Specifically, complete recovery occurred in 72% of cases, with about 54% of patients surviving for several years. Additionally, selecting CD34+ cells can help reduce complications like GvHD, a common issue in transplants. These findings offer hope for better survival rates and fewer complications for patients undergoing stem cell transplants. ^{1 6 7 8 9}

Who Is on the Research Team?

Guenther Koehne, MD, PhD

Principal Investigator

Baptist Health South Florida/Miami Cancer Institute

Are You a Good Fit for This Trial?

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

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.

My heart, liver, kidneys, and lungs are all functioning well.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12331545/

Impact of CD34+ cell dose on outcomes of haploidentical ... Several studies, particularly in the context of HLA-matched transplantation, have reported that higher CD34+ cell doses may improve outcomes by ...

2. 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%.

3. astctjournal.org astctjournal.org/article/S2666-6367(22)01831-0/fulltext

Effect of CD34 + Cell Dose on the Outcomes of Allogeneic ... CD34+ cell dose did not impact survival outcomes after matched sibling donor, matched unrelated donor, and mismatched unrelated donor allogeneic ...

4. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/4586/424634/CD34-Cell-Dose-Effects-on-Clinical-Outcomes-of

CD34+ Cell Dose Effects on Clinical Outcomes of Patients ... After a median follow-up of 23.3 months (range, 12.1-41.8) 2-year overall survival (OS) was 64.5 % (95% CI 59.3-69.7) with a leukemia-free ...

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

Allogeneic Stem Cell Transplantation with CD34+ ... T cell depletion through positive selection of CD34+ cells has emerged as a promising strategy to reduce acute and chronic GvHD in these patients.

6. astctjournal.org astctjournal.org/article/S1083-8791(20)30461-4/fulltext

Addition of Thiotepa to Total Body Irradiation and ... Thiotepa is safe to use with a total body irradiation (TBI)/cyclophosphamide backbone in pediatric patients with acute lymphoblastic leukemia, with no increase ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3673764/

A Novel Reduced Intensity Conditioning Regimen Induces a ... We evaluated double-unit CB transplantation (CBT) in 30 patients (median age 56 years range 18–69) with acute leukemia or myelodysplasia using a regimen of ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497120574351

Transplantation of highly purified CD34+ progenitor cells ... The 2-year survival estimate was 38% for all patients and 63% for patients with ALL in complete remission. Patients with myeloid malignancies had a poor outcome ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123135609

Clinical Outcomes of Allogeneic Hematopoietic Stem Cell ... The median follow-up time was 24 months (2-84 months), and all 37 cases survived the graft, with a median leukocyte engraftment of +13 days (9-21 days), and a ...