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

Trial Summary

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.

What data supports the effectiveness of the treatment Cyclophosphamide, Fludarabine, and Thiotepa for blood cancers?

Research shows that using Cyclophosphamide, Fludarabine, and Thiotepa in cord blood transplants can lead to high rates of successful engraftment (when transplanted cells start to grow and make healthy blood cells) and improved survival rates in patients with blood cancers. These drugs, when used together, have been associated with lower relapse rates and better overall survival compared to some other treatment regimens. ^{1 2 3 4 5}

Is cord blood transplantation safe for treating blood cancers?

Cord blood transplantation has been studied for safety, showing that while it can lead to complications like graft-versus-host disease (a condition where the donor cells attack the recipient's body) and organ toxicity, many patients achieve successful engraftment (when the transplanted cells start to grow and make healthy blood cells). Treatment-related deaths can occur, but survival rates are promising, indicating it is generally safe with careful monitoring. ^{2 3 5 6 7}

How is the cord blood transplantation treatment with Cyclophosphamide, Fludarabine, and Thiotepa different from other treatments for blood cancers?

This treatment is unique because it uses umbilical cord blood from unrelated donors, which can be an option for patients who do not have a matched donor. The combination of Cyclophosphamide, Fludarabine, and Thiotepa is part of a conditioning regimen that prepares the body for the transplant, aiming to improve survival rates in patients with advanced blood cancers. ^{2 8 9 10 11}

What is the purpose of this trial?

The goal of this clinical research study is to learn if intermediate-intensity conditioning therapy followed by a cord blood transplant can help to control high-risk hematological malignancies in patients who need a second allogeneic stem cell transplantation.

Research Team

Warren Fingrut, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

References

1. Italy 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. [2021]

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

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. [2021]

3. United States 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. [2020]

4. United States 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. [2019]

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

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning. [2018]

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

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. [2013]

7. United States 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. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation from unrelated donors in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. [2022]

9. Switzerland 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. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

Reduced-intensity conditioning followed by unrelated umbilical cord blood transplantation for advanced hematologic malignancies: rapid engraftment in bone marrow. [2018]

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

Single-unit umbilical cord blood transplantation from unrelated donors in adult patients with chronic myelogenous leukemia. [2010]