Stem Cell Transplant for Leukemia

(HAPLOTAB Trial)

Not currently recruiting at 1 trial location

Overseen By Erin Morales, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must not be taking: Immunosuppressive treatments

Disqualifiers: Severe cardiac, renal, pulmonary, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to find a safer method for performing stem cell transplants in individuals with certain blood disorders, such as leukemia and sickle cell disease. Researchers seek to reduce the risk of graft versus host disease (GvHD), a serious post-transplant complication, by using a special technique to treat donor cells called Haploidentical Hematopoietic Cell Transplantation. This approach could decrease the need for immune-suppressing drugs after the transplant. Ideal candidates for this trial include those with specific blood conditions who lack a perfectly matched donor. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could enhance future transplant safety.

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

The trial protocol does not specify if you need to stop taking your current medications. However, since this is a stem cell transplant study, it's possible that some medications might need to be adjusted or stopped. Please consult with the trial coordinators or your doctor for specific guidance.

What prior data suggests that the CliniMACS® TCRα/β-Biotin System is safe for use in stem cell transplantation?

Research has shown that the CliniMACS TCRα/β-Biotin System, used in this stem cell transplant process, reduces unwanted T cells, which can cause complications. Studies indicate that this system leads to better immune recovery compared to other methods, allowing patients to regain a stronger immune system more quickly after the transplant.

In haploidentical hematopoietic cell transplantation (a type of stem cell transplant from partially matched donors), research has shown promising safety results. Specifically, one study found that about 96.4% of patients successfully achieved neutrophil engraftment, meaning the transplanted cells began to grow and produce healthy blood cells—a crucial step for recovery.

Overall, the treatment appears well-tolerated with good safety outcomes. However, as this is an early-phase study, more research is needed to fully confirm safety in larger groups of people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about haploidentical hematopoietic cell transplantation for leukemia because it offers a new way to use stem cells that might overcome some limitations of current therapies. Unlike standard treatments like chemotherapy or fully matched donor transplants, this method uses a donor who is only a partial match, which can significantly widen the pool of available donors. Additionally, the process involves a special treatment of the donor's blood cells, specifically depleting certain T cells while enriching stem cells, which might reduce the risk of complications like graft-versus-host disease. This innovative approach could make stem cell transplants more accessible and safer for more leukemia patients.

What evidence suggests that the CliniMACS® TCRα/β-Biotin System is effective for reducing GvHD in leukemia patients?

Research has shown that the CliniMACS TCRα/β-Biotin System for stem cell transplants, part of this trial, can improve immune recovery. This method removes certain immune cells that might cause issues post-transplant. Studies have found early signs of strong immune system recovery, with important immune cells returning to good levels within six weeks.

Additionally, haploidentical hematopoietic cell transplantation, another treatment option in this trial, has shown promising results. One study found a 60% overall survival rate in leukemia patients who received this transplant. Another study reported a high survival rate of over 80% at three years, which is very encouraging. Together, these treatments suggest they can effectively support recovery from leukemia while reducing risks like graft versus host disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Erin Morales, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients without a fully matched donor or with rapidly progressing diseases who need a stem cell transplant. It's open to those with certain blood cancers, hemoglobin disorders like thalassemia or sickle cell disease, severe viral infections, immune deficiencies, and bone marrow failures. Participants must be in good enough health to undergo the procedure.

Inclusion Criteria

I don't have a perfect match donor or my disease is progressing too quickly to wait for one.

Signed written informed consent

I am mostly active and can do things for myself.

Exclusion Criteria

My heart is weak, with an ejection fraction below 40%.

I do not have any serious uncontrolled health or mental conditions.

I am currently on immunosuppressive drugs for GVHD from a past transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants undergo a conditioning regimen with chemotherapy, with or without radiation, prior to transplantation

1-2 weeks

Transplantation

Participants receive a donor stem cell transplant with TCR Alpha/Beta+ and CD19+ depletion

1 day

Engraftment Monitoring

Participants are monitored for neutrophil and platelet engraftment

42 days

Acute GVHD Monitoring

Participants are monitored for acute graft versus host disease

100 days

Follow-up

Participants are monitored for chronic GVHD, overall survival, and transplant-related mortality

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• CliniMACS® TCRα/β-Biotin System
• Haploidentical Hematopoietic Cell Transplantation

Trial Overview The study tests a new way of doing transplants using half-matched family donors' blood cells treated to reduce GvHD risk. The treatment uses CliniMACS® TCRα/β-Biotin System to remove specific immune cells that could cause complications post-transplant.

How Is the Trial Designed?

Group I: Alpha beta+ T cell depleted CD34+ stem cells Experimental Treatment 1 Intervention

The patient will be receiving a donor stem cell transplant with a preceding conditioning regimen (chemotherapy with, or without, radiation). The investigators will be specially treating the donor's blood cells used for the stem cell transplant.

Haploidentical Hematopoietic Cell Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Haploidentical Hematopoietic Stem Cell Transplant for:

• Severe Aplastic Anemia
• Hematological Malignancies
• Immunodeficiency Disorders

Approved in European Union as Haploidentical Hematopoietic Stem Cell Transplant for:

• Severe Aplastic Anemia
• Acute Leukemia
• Chronic Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Haploidentical hematopoietic stem cell transplantation (HSCT) using granulocyte colony-stimulating factor (G-CSF) primed bone marrow and peripheral blood grafts has proven effective for treating acute leukemia and chronic myeloid leukemia, based on a nine-year experience without the need for T cell depletion.

This method has also shown promise in treating intermediate and high-risk myelodysplastic syndrome and severe aplastic anemia, with improved immune recovery linked to better transplant outcomes, although managing chronic graft-vs.-host disease remains crucial for patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem cell transplantation without in vitro T-cell-depletion for the treatment of hematologic diseases. Huang, XJ.[2021]

Genetically haploidentical stem cell transplants are a viable option for patients with advanced acute leukemia who lack a compatible sibling donor, providing immediate availability for most patients.

Recent advancements in techniques have improved clinical outcomes, reducing issues like graft-versus-host disease and engraftment failure, making haploidentical transplants a promising alternative to matched unrelated donor transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetically haploidentical stem cell transplantation for acute leukemia. Rowe, JM., Lazarus, HM.[2005]

Haploidentical stem cell transplantation (haplo-SCT) is a viable option for high-risk leukemia patients without matched donors, showing comparable outcomes to other transplantation methods like matched sibling donor and umbilical cord blood transplants.

Innovative strategies, such as co-transplanting haploidentical allografts with cord blood, have demonstrated feasibility and potential to enhance treatment effectiveness by reducing relapse rates after haplo-SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for the treatment of leukemia: current status. Chang, YJ., Wang, Y., Huang, XJ.[2014]

Haploidentical hematopoietic stem cell transplant (HSCT) with posttransplant cyclophosphamide (PTCy) is a safe and effective treatment for children with acute leukemia, showing an overall survival rate of 70.5% and event-free survival of 64.7% based on a study of 17 children.

Myeloablative conditioning improved disease-free survival, while chronic graft-versus-host disease (GVHD) was associated with better outcomes, as most patients who developed chronic GVHD remained alive and disease-free.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Stem Cell Transplantation With Post-transplant Cyclophosphamide for Pediatric Acute Leukemia is Safe and Effective. Sharma, A., Rastogi, N., Chatterjee, G., et al.[2022]

In a study of 13 patients with nonmalignant hematologic diseases, HLA haploidentical stem cell transplantation demonstrated effective engraftment and resulted in 11 patients surviving free of disease after a median follow-up of 13 months.

The procedure showed a manageable safety profile, with low incidences of acute and chronic graft-versus-host disease (GVHD), indicating that it is a viable treatment option for conditions like severe aplastic anemia and β thalassemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The outcome of thirteen patients with nonmalignant hematologic diseases treated with HLA haploidentical stem cell transplantation]. Tao, Y., Wu, B., Du, Q., et al.[2018]

Hematopoietic stem cell transplantation from HLA-haploidentical family members can provide a potential cure for patients lacking HLA-matched donors, with techniques like ex vivo T-cell depletion leading to successful donor engraftment and reduced acute graft-versus-host disease.

Despite these advancements, challenges such as delayed immune reconstitution and high relapse rates remain, prompting research into innovative strategies like donor lymphocyte infusions and modified natural killer cell therapies to enhance post-transplant recovery and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical transplantation for leukemia. Kanda, J., Chao, NJ., Rizzieri, DA.[2021]

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) shows promise as an alternative treatment for high-risk acute leukemia patients who do not have a matched donor, with a 91% engraftment rate observed in a study of 266 patients.

The 2-year leukemia-free survival rates varied significantly based on the patient's remission status at the time of transplantation, highlighting that those in complete remission (CR1) had the best outcomes, with a 48% survival rate for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Ciceri, F., Labopin, M., Aversa, F., et al.[2021]

HLA haploidentical peripheral blood stem cell transplantation showed promising results in treating 30 patients with refractory leukemia, with 27 patients achieving complete remission after the procedure.

While the therapy can lead to disease-free survival in some patients, there were significant risks, including severe acute graft versus host disease in six patients, highlighting the need for careful monitoring and management post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The outcomes of the thirty patients with refractory leukemia treated with related HLA haploidentical stem cells transplantation]. Wu, BY., Guo, KY., Song, CY., et al.[2014]

Haploidentical transplantation from mismatched family donors is a viable option for high-risk acute leukemia patients lacking a matched donor, showing favorable event-free survival compared to other stem cell sources.

The strategy of using high numbers of T-cell-depleted hematopoietic progenitor cells without post-transplant immunosuppression effectively manages graft rejection and graft-versus-host disease, while also emphasizing the importance of natural killer cell activity in preventing leukemia relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity. Aversa, F., Martelli, MF., Velardi, A.[2012]

In a study of 195 adult patients with acute lymphoblastic leukemia (ALL) who underwent haploidentical hematopoietic cell transplantation (haplo-HCT), the 2-year overall survival rate improved significantly from 53.5% (2011-2015) to 75.5% (2016-2018), indicating better outcomes with more recent transplantations.

While the incidence of acute graft-vs-host disease (GVHD) increased from 26.4% to 42% in the later group, the risk of nonrelapse mortality (NRM) decreased significantly, suggesting that posttransplantation cyclophosphamide is becoming a safer and more effective option for ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of T-cell-replete haploidentical stem cell transplantation improves with time in adults with acute lymphoblastic leukemia: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Nagler, A., Labopin, M., Koc, Y., et al.[2022]

Hematopoietic stem cell transplantation (HSCT) from HLA haploidentical family donors has shown promise for treating high-risk blood cancers, with studies at San Raffaele Scientific Institute demonstrating effective immune reconstitution and control of graft-versus-host disease (GvHD) using T cell-depleted transplants followed by genetically modified donor T cells.

Current trials, including a phase III study (TK008), are evaluating the safety and efficacy of these approaches, particularly focusing on advanced leukemia patients receiving unmanipulated peripheral blood stem cells (PBSCs) with a sirolimus-based GvHD prophylaxis, indicating a significant advancement in transplant strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical HSCT: a 15-year experience at San Raffaele. Bonini, C., Peccatori, J., Stanghellini, MT., et al.[2018]

Citations

1. static.miltenyibiotec.com static.miltenyibiotec.com/asset/150655405641/document_c3dunu39b94hv7qotihs2f4m00?content-disposition=inline

CliniMACS ® TCRα/β-Biotin System BMT 2015 Mar;50 Suppl1: 462. Use of TCRαβ/CD19 depletion results in superior immune recovery compared to CD34 selection after transplantation of haploidentical ...

2. miltenyibiotec.com miltenyibiotec.com/US-en/products/clinimacs-tcra-b-product-line.html

CliniMACS® TCRα/β Product Line After labeling of TCRα/β+ cells with CliniMACS TCRα/β-Biotin, CliniMACS Anti-Biotin Reagent is used for the magnetic depletion of TCRα/β+ cells from the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7848723/

Automated generation of gene-edited CAR T cells at clinical ... During the TCRα/β depletion process, the cells were labeled and magnetically selected with CliniMACS TCRα/β-biotin and CliniMACS anti-biotin reagents ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04249830

NCT04249830 | Stem Cell Transplant From Donors After ... The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or ...

5. patents.google.com patents.google.com/patent/US20140308250A1/en

Cell preparations depleted of tcr alpha/beta The use of TCR alpha/beta depletion strategy results in an early immune reconstitution with values of more 100 CD4 cells/μl within six weeks after the ...

6. cdn.ymaws.com cdn.ymaws.com/www.cttcanada.org/resource/resmgr/website_docs/CliniMACS%C2%AE_Plus_System_User_.pdf

CliniMACS® Plus System User Manual (Canadian edition) TCRα/β is expressed on the majority of peripheral blood T cells. The CliniMACS Plus TCRα/β-Biotin System uses murine mono- clonal antibodies specific for ...