Cord Blood Transplantation for Blood Cancers

Overseen By Warren Fingrut, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Myelofibrosis, Two prior transplants, 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

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a specific combination of medications, followed by a cord blood transplant, can control certain blood cancers that have returned after an initial stem cell transplant. The treatment uses drugs like Cyclophosphamide, Fludarabine, and Thiotepa, which prepare the body for the transplant. This study may suit individuals who have experienced a relapse of blood cancer after a previous stem cell transplant. Participants should have specific types of leukemia or myelodysplastic syndromes and be in remission or have low cancer cell levels. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that a combination of cyclophosphamide, fludarabine, and thiotepa has been studied for safety in patients needing cord blood transplants. In one study, patients who received these treatments faced some risks but also experienced promising outcomes. High doses of cyclophosphamide were linked to a higher chance of death not caused by cancer returning and lower survival rates at 180 days. However, with careful monitoring, this approach remains manageable.

Another study suggested that adjusting the doses of these drugs can enhance safety while maintaining effectiveness. This means the treatment plan can be modified to reduce side effects. Overall, while some risks exist, this combination has been used in various settings with close attention to patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Optimized Cord Blood Transplantation (CBT) for blood cancers because it offers a unique approach compared to current treatments like chemotherapy and traditional stem cell transplants. Unlike these standard options, CBT utilizes stem cells from umbilical cord blood, which are easier to match with patients and can potentially lead to fewer complications. Additionally, the combination of cyclophosphamide, fludarabine, and thiotepa in this treatment aims to enhance the effectiveness of the transplant and improve patient outcomes. This innovative approach could provide new hope for patients who struggle to find suitable stem cell donors.

What evidence suggests that this trial's treatments could be effective for high-risk hematological malignancies?

Research has shown that a combination of three drugs—cyclophosphamide, fludarabine, and thiotepa—can be promising for treating blood cancers. In this trial, participants will receive cord blood transplants with these drugs as part of the "Optimized CBT" treatment arm. Studies have found that patients receiving this combination achieved excellent results. This treatment plan prepares the body for a successful transplant without being too harsh. Previous trials demonstrated that this combination can effectively manage high-risk blood cancers. Overall, the evidence supports its potential effectiveness in treating these challenging conditions. ^{1 3 4 5 6}

Who Is on the Research Team?

Warren Fingrut, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 0-60 with high-risk blood cancers who have relapsed after their first stem cell transplant. They must be in good physical condition, with a Karnofsky score of at least 70%, proper heart and kidney function, and specific diagnoses like AML or ALL in remission. Pregnant individuals, those not using contraception, or with uncontrolled infections/GVHD can't participate.

Inclusion Criteria

Left ventricular ejection fraction (MOD-bp) > 50%

I am mostly able to care for myself but may need help.

My kidneys work well (creatinine clearance over 50 ml/min).

Exclusion Criteria

Pregnant or breastfeeding

I have an ongoing and uncontrolled infection.

Women of child-bearing potential and men not using adequate contraception

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Therapy

Participants receive intermediate-intensity conditioning therapy prior to cord blood transplant

2-3 weeks

Cord Blood Transplantation

Participants undergo cord blood transplantation to control high-risk hematological malignancies

1 week

Follow-up

Participants are monitored for safety, effectiveness, and adverse events after transplantation

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Thiotepa

Trial Overview

The study tests if intermediate-intensity conditioning therapy followed by cord blood transplantation can control high-risk hematological malignancies in patients needing a second allogeneic stem cell transplant. Drugs used include Cyclophosphamide, Thiotepa, Mycophenolate mofetil, Fludarabine, and Tacrolimus.

How Is the Trial Designed?

Group I: Optimized CBT Experimental Treatment 5 Interventions

Participants enrollment on trial will be determined by consultation with the physicians of the SCT Service.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a study of 81 patients with hematological diseases undergoing unrelated umbilical cord blood transplantation (UCBT), 96.3% achieved complete engraftment, indicating high efficacy of the treatment protocol.

The combination of high-dose cyclophosphamide and fludarabine conditioning before UCBT was effective in enhancing stem cell engraftment and improving overall survival rates, which were reported at 80.2% by the end of follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Conditioning Regimen Can Significantly Promote Post-Transplant Immune Reconstitution and Improve the Outcome of Umbilical Cord Blood Transplantation for Patients. Yu, ZP., Ding, JH., Sun, AN., et al.[2020]

Umbilical cord blood transplantation from unrelated donors shows promising outcomes for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, with a 5-year overall survival rate of 44% among 45 patients studied.

The study found a high rate of myeloid engraftment at 96% within a median of 20 days, indicating effective transplantation, although there were notable risks of graft-versus-host disease and treatment-related mortality at 31% and 17% respectively by day +100.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Piñana, JL., Sanz, J., Picardi, A., et al.[2022]

In a clinical trial involving 113 patients, sequential haploidentical cord blood transplantation (haplo-cord HSCT) showed improved overall survival (OS) and disease-free survival (DFS) in patients with relapsed/refractory hematologic malignancies compared to single umbilical cord blood transplantation (UCBT).

The 2-year survival probabilities for haplo-cord HSCT were significantly higher (64.9% OS and 64.5% DFS) compared to single UCBT (31.6% OS and 31.6% DFS), indicating that haplo-cord HSCT may be a promising alternative for patients lacking HLA-identical donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies. Li, H., Li, X., Chen, Y., et al.[2021]

In a study of 12 patients with advanced hematologic malignancies, reduced-intensity conditioning followed by cord blood transplantation (CBT) showed promising early engraftment, with 6 patients achieving complete donor chimerism by day 14.

Despite the initial success in engraftment, there was a significant risk of transplantation-related mortality, with 4 out of 11 patients experiencing complications related to platelet recovery, highlighting the need for careful monitoring and management post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow. Misawa, M., Kai, S., Okada, M., et al.[2018]

In a study of 89 hematopoietic cell transplantation recipients, higher levels of the active metabolite of cyclophosphamide (PM AUC0-8 hr) were linked to worse nonrelapse mortality and overall survival, indicating that careful monitoring of this metabolite is crucial for patient outcomes.

Patients with low levels of the active metabolite of fludarabine (F-ara-ADay-4) and low PM AUC0-8 hr had significantly lower nonrelapse mortality, suggesting that optimizing drug exposure could improve safety and efficacy in reduced-intensity conditioning regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Fludarabine and Cyclophosphamide Exposures Lead to Worse Outcomes in Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Adult Hematologic Malignancy. Takahashi, T., Scheibner, A., Cao, Q., et al.[2021]

In a study of 99 adult patients undergoing double-unit cord blood transplantation, an intensified reduced-intensity conditioning (RIC) regimen showed a significantly lower relapse rate compared to the standard RIC regimen, indicating improved efficacy in preventing cancer recurrence.

The intensified RIC regimen also resulted in significantly better overall survival rates without increasing transplant-related mortality, suggesting it may be a safer and more effective option for older patients with acute myelogenous leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thiotepa-Based Intensified Reduced-Intensity Conditioning Adult Double-Unit Cord Blood Hematopoietic Stem Cell Transplantation Results in Decreased Relapse Rate and Improved Survival Compared with Transplantation Following Standard Reduced-Intensity Conditioning: A Retrospective Cohort Comparison. Sharma, P., Pollyea, DA., Smith, CA., et al.[2019]

A modified myeloablative regimen using thiotepa, TBI, and fludarabine in 31 adult patients resulted in a high neutrophil engraftment rate of 90% by 60 days, indicating improved engraftment while reducing treatment-related mortality (TRM) to 30% at 3 years.

The study also reported manageable rates of acute and chronic graft-versus-host disease (GVHD), with 45% experiencing grades II to IV acute GVHD by day 100 and 40% developing chronic GVHD by 2 years, suggesting that this regimen is a promising alternative for umbilical cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning. Anand, S., Thomas, S., Corbet, K., et al.[2018]

In a study involving three children with refractory severe aplastic anemia (SAA), a radiotherapy-free conditioning regimen using fludarabine and other agents was effective in preparing them for hemopoietic cell transplantation (HCT) without the development of graft-versus-host disease (GVHD).

All patients achieved normal blood counts and complete donor chimerism after the transplant, demonstrating that fludarabine-based conditioning can be a safe and effective option for children undergoing HCT from alternative donors, even after previous transplant failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Urban, C., Benesch, M., Sykora, KW., et al.[2013]

In a study of 26 adults with chronic myelogenous leukemia (CML) receiving umbilical cord blood transplantation (UCBT), the treatment showed a promising overall disease-free survival rate of 41% after 8 years, with 59% for patients in the first or second chronic phase.

The study highlighted that higher doses of CD34(+) cells improved myeloid engraftment rates to 88%, but treatment-related mortality was significantly higher for patients in advanced disease phases, indicating the need for better patient selection and supportive care to enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-unit umbilical cord blood transplantation from unrelated donors in adult patients with chronic myelogenous leukemia. Sanz, J., Montesinos, P., Saavedra, S., et al.[2010]

In a multicenter phase II study involving 53 patients, double umbilical cord blood transplantation showed a high engraftment rate of 92% with a median neutrophil recovery time of 36 days, indicating its efficacy in treating high-risk hematological malignancies.

The study found that early CD4(+) T-cell chimerism can predict the survival of the transplanted units, suggesting that CD4(+) lymphocytes may play a role in the success of the transplantation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study. Somers, JA., Braakman, E., van der Holt, B., et al.[2021]

A conditioning regimen using melphalan, thiotepa, fludarabine, and rabbit antithymocyte globulin (FMT) was evaluated in 47 patients with advanced hematologic malignancies, showing that 91% of patients successfully engrafted neutrophils after a median of 22 days, indicating effective hematopoietic recovery.

Despite a significant incidence of grade 3 gastrointestinal toxicity (32%) and a cumulative incidence of acute and chronic graft-versus-host disease (53% and 34%, respectively), the two-year disease-free survival rate was 31% and overall survival rate was 44%, suggesting that FMT is a feasible and potentially effective conditioning regimen for unrelated cord blood transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Ciurea, SO., Saliba, RM., Hamerschlak, N., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

A Novel Reduced Intensity Conditioning Regimen Induces a ...

Conditioning consisted of cyclophosphamide 50 mg/kg (day -6), fludarabine 30 mg/m2/day × 5 (days -6 to -2), thiotepa 5 mg/kg/day × 2 (days -5, -4), and total ...

2.

cancernetwork.com

cancernetwork.com/view/ucbt-yields-excellent-efficacy-outcomes-in-hematologic-malignancies

UCBT Yields Excellent Efficacy Outcomes in Hematologic ...

“Data from this prospective trial demonstrated excellent outcomes for cord blood transplant recipients receiving myeloablative conditioning in ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00719888?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DAY-101)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL))&rank=10

Study Details | Umbilical Cord Blood Transplant ...

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636721009325

Higher Fludarabine and Cyclophosphamide Exposures ...

High cyclophosphamide (Cy) exposure was associated with worse day 100 and day 180 nonrelapse mortality (NRM) and worse day 180 overall survival (OS).

5.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/2131/529702/A-Phase-II-Study-of-Low-Dose-Melphalan-with

A Phase II Study of Low Dose Melphalan with Thiotepa and ...

We hypothesized that reducing the dose of melphalan when combining with thiotepa and fludarabine can be a safe and effective reduced intensity ...

6.

astctjournal.org

astctjournal.org/article/S2666-6367(21)00932-5/fulltext

Higher Fludarabine and Cyclophosphamide Exposures ...

High cyclophosphamide (Cy) exposure was associated with worse day 100 and day 180 nonrelapse mortality (NRM) and worse day 180 overall survival (OS).