Haploidentical Transplant for Blood Disorders

Overseen By Derek Schatz

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Disqualifiers: HLA identical donor, others

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

Approved in 1 Jurisdiction 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?

This trial explores a new method for performing stem cell transplants in individuals with serious blood disorders. It combines specially selected cells from a family donor with umbilical cord blood to determine if this approach enhances the transplant process and safety. The trial seeks participants with serious blood conditions requiring a stem cell transplant who lack a perfectly matched family donor. Participants should have a family member who is a partial match and be able to locate a suitable umbilical cord blood unit. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could improve transplant options for future patients.

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

The trial protocol does not specify whether you need to stop taking your current medications.

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 Miltenyi CliniMACS® CD34 Reagent System is safe for promoting engraftment in haploidentical transplants?

Research shows that the Miltenyi CliniMACS® CD34 Reagent System, part of the treatment under study, is designed to safely increase the number of CD34+ cells, which are special stem cells used in transplants. Previous studies have demonstrated that this system effectively removes T-cells, potentially reducing the risk of graft-versus-host disease (GvHD), a condition where transplanted cells attack the body.

Another study found that the system efficiently collects the necessary CD34+ cells, suggesting that the treatment can be well-tolerated by the body. However, since this treatment is in an early phase, less information is available about its safety in humans compared to later phases. This is important to consider when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the haploidentical CD34+ selected cells combined with a single unit umbilical cord blood transplant because it offers a novel approach to treating blood disorders. Unlike traditional treatments, which often use fully matched donors, this method allows for the use of partially matched (haploidentical) donors, expanding the pool of potential donors significantly. Furthermore, the use of CD34+ cell selection and T-cell depletion aims to reduce the risk of graft-versus-host disease, a common complication in transplants. The combination with umbilical cord blood provides a unique synergy that may improve engraftment and recovery times, potentially leading to better outcomes for patients.

What evidence suggests that the Miltenyi CliniMACS® CD34 Reagent System is effective for high-risk hematologic disorders?

In this trial, participants will receive a transplant using the Miltenyi CliniMACS® CD34 Reagent System, which studies have shown helps transplanted cells grow and produce healthy blood cells. This system is used with a single unit of umbilical cord blood. Previous patients who received this combination treatment demonstrated promising results, with a good rate of new blood cell growth. This indicates the treatment effectively aids people with serious blood disorders. These findings suggest the treatment benefits those needing a transplant when a fully matched donor is unavailable. ^{1 4 6 7 8}

Who Is on the Research Team?

Jonathan Gutman, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with high-risk blood disorders who lack an exact HLA-matched donor but have a partially matched (5/10 to 8/10) relative and a suitable umbilical cord blood unit. It's not open to those with a fully matched (6/6) related donor or who don't meet standard transplant guidelines.

Inclusion Criteria

I have a cord blood match with at least 4/6 HLA compatibility and enough cells for my body weight.

I have a family donor who is a partial match for a stem cell transplant.

I understand the treatment I will be receiving.

Exclusion Criteria

I have a family donor who is a perfect match for my transplant.

Any patient not meeting institutional standard guidelines for transplant eligibility

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Recipients receive a standard conditioning regimen before transplantation

1 week

Transplantation

Participants receive an allograft containing donor CD34+ cells and a single UCB unit

Day 0

Engraftment Monitoring

Participants are monitored for successful engraftment and treatment-related serious adverse events

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant
• Miltenyi CliniMACS® CD34 Reagent System

Trial Overview The study tests the Miltenyi CliniMACS® CD34 Reagent System, aiming to improve how well patients accept stem cells from partly matched relatives combined with umbilical cord blood transplants in treating serious blood diseases.

How Is the Trial Designed?

Group I: Miltenyi CliniMACS® CD34 Reagent System Experimental Treatment 1 Intervention

The haploidentical donor will be mobilized by G-CSF and undergo one apheresis to collect CD34+ selected stem cell product after Miltenyi CliniMACS® CD34+ selection. The products will be cryopreserved until the time of transplantation. Recipients will receive a standard conditioning regimen. After the conditioning regimen, the subjects will receive an allograft on day 0 containing donor CD34+ cells that have been positively selected and T-cell depleted following G-CSF mobilization combined with a single UCB unit. UCB unit will not be manipulated, and will be prepared and infused separately following standard of care procedure.

Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant is already approved in United States for the following indications:

Approved in United States as CliniMACS CD34 Reagent System for:

• Processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-identical, sibling donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional graft versus host disease (GVHD) prophylaxis in patients with acute myeloid leukemia (AML) in first morphologic complete remission.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes was performed on four Mexican children with hematological malignancies, showing successful engraftment in three out of four cases over a follow-up period of 9½ years.

Despite the successful engraftment, all patients experienced cytomegalovirus reactivation, and one child died due to graft rejection and infectious complications, highlighting the significant risk of infections associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical bone marrow transplantation in Mexico. Vázquez-Meraz, JE., Arellano-Galindo, J., Mendoza-García, E., et al.[2012]

Umbilical cord blood (UCB) and haploidentical transplantation are promising alternatives for allogeneic hematopoietic stem cell transplantation, especially in the diverse Asia Pacific region where donor registries are limited.

Successful donor selection for these transplantation methods depends on various factors, including HLA mismatches, ABO compatibility, and specific characteristics like donor age and CMV serology, which are crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate Donor Transplantation. Hwang, WY., Kongtim, P., Majhail, NS., et al.[2023]

Haploidentical related donors provide a valuable alternative for stem cell transplantation, especially for patients lacking HLA-matched donors, due to their immediate availability and ease of procurement.

Current strategies to overcome the histoincompatibility barrier in haploidentical stem cell transplants have shown promising clinical results, making this approach increasingly viable compared to umbilical cord blood transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies in haploidentical stem cell transplantation in adults. Bayraktar, UD., Ciurea, SO.[2021]

Haplo-cord transplantation using CD34+-selected partially matched unrelated donor grafts allows for rapid engraftment in patients lacking a suitable haploidentical donor, with 83% achieving cord blood unit (CBU) engraftment by day +60.

The procedure demonstrated a manageable safety profile, with a 27% incidence of grade 2-4 acute graft-versus-host disease (GVHD) and a 4% incidence of chronic GVHD at one year, while achieving an overall survival rate of 54% at one year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplants supported by unrelated donor CD34+ progenitor cells. Gomez-Arteaga, A., Orfali, N., Guarneri, D., et al.[2021]

In a study of 550 unrelated cord blood transplants (UCBTs) for hematologic malignancies, both the nucleated cell (NC) dose before freezing and the number of HLA disparities significantly influenced patient outcomes, including neutrophil and platelet recovery.

The overall 3-year survival rate was 34.4%, with key prognostic factors for survival being the recipient's age, gender, and disease status, suggesting that optimizing donor selection based on these factors could improve transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Gluckman, E., Rocha, V., Arcese, W., et al.[2019]

In a study involving two children with acute lymphoblastic leukemia, HLA one locus mismatched umbilical cord blood transplantation led to earlier and more durable hematopoietic and immunologic reconstitution, with significant recovery markers observed by day 60 and day 134.

The transplantation resulted in milder complications, with only grade II acute graft versus host disease (aGVHD) occurring, and both patients survived for over 250 days post-transplant, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of two case childhood acute lymphoblastic leukemia by HLA-mismatched unrelated umbilical cord blood transplantation]. Sun, Z., Wang, Z., Zhu, W., et al.[2016]

Transplanting two units of umbilical cord blood (UCB) simultaneously can enhance hematopoietic reconstitution in adults, as demonstrated in a patient with advanced acute lymphocytic leukemia who achieved complete remission without graft-versus-host disease.

Both UCB units contributed to blood cell production, showing double chimerism, which suggests that this method could improve outcomes for adult patients who do not have a compatible donor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-chimaerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. De Lima, M., St John, LS., Wieder, ED., et al.[2019]

The study successfully created a novel Human Multi-Chimeric Cell (HMCC) line by fusing umbilical cord blood cells from three unrelated donors, which may offer a new therapeutic approach for inducing transplant tolerance without the need for lifelong immunosuppression.

HMCC demonstrated safety with no genotoxicity, maintained viability, and showed clonogenic properties, indicating its potential effectiveness for bone marrow and solid organ transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Multi-Chimeric Cell (HMCC) Therapy as a Novel Approach for Tolerance Induction in Transplantation. Siemionow, M., Cwykiel, J., Brodowska, S., et al.[2023]

In a review of 280 patients who underwent double umbilical cord blood transplantation (UCBT), only 4% (11 patients) maintained mixed-unit chimerism for at least one year, suggesting that sustained hematopoiesis typically comes from a single donor unit.

Mixed-unit chimerism was more likely when both cord blood units were closely matched for HLA, and while there may be potential benefits for enhancing the graft-versus-leukemia effect, more extensive studies are needed to determine its overall impact on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double umbilical cord blood transplantation: relevance of persistent mixed-unit chimerism. Hashem, H., Lazarus, HM.[2015]

Haploidentical hematopoietic stem cell transplant (HSCT) offers a promising alternative for patients lacking fully HLA-matched donors, with improved outcomes over the past decade.

Despite initial high mortality rates due to graft rejection and severe graft-versus-host disease, advancements in techniques have enhanced the safety and efficacy of haploidentical HSCT, making it a viable option for treating various hematologic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of the progress on haploidentical hematopoietic transplantation. Farhadfar, N., Hogan, WJ.[2020]

Umbilical cord blood transplants are a valuable alternative for treating blood cancers, offering rapid availability and less strict matching requirements, which can reduce the risk of relapse and graft-versus-host disease.

Double-unit umbilical cord blood transplants may improve neutrophil recovery rates and address the issue of limited cell doses, especially in adult patients, while also serving as a platform for testing new expansion and homing techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should double cord blood transplants be the preferred choice when a sibling donor is unavailable? Wagner, JE.[2021]

Hematopoietic cell transplantation (HCT) has greatly improved with the use of alternative donors, allowing about 75% of patients without an HLA-matched sibling to access potentially curative transplants.

Umbilical cord blood (UCB) offers advantages like ready availability and lower risk of graft-versus-host disease (GVHD), but has slower recovery times, while haploidentical donors provide immediate availability but come with higher GVHD risks and challenges in immune recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The great debate: haploidentical or cord blood transplant. Ballen, KK., Spitzer, TR.[2011]

Haploidentical stem cell transplantation (SCT) from a parent is now a viable option for children with leukemia, providing comparable survival rates to unrelated donor transplants, thanks to advances in technology that reduce graft rejection and severe complications.

Despite the promise of haploidentical SCT, challenges such as post-transplant infections and leukemia relapse remain, highlighting the need for further research into adoptive cellular immunity to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of haploidentical stem cell transplantation in the management of children with haematological disorders. Veys, P., Amrolia, P., Rao, K.[2019]

In a study of 620 acute leukemia cases treated with umbilical cord blood transplantation, a lower CD34+ cell dosage of <0.83 × 10^5/kg was found to be acceptable for patients with an HLA mismatch of ≤3/10, suggesting that current guidelines may be too strict.

The study also revealed that specific donor KIR haplotypes can provide protection against relapse-related mortality, indicating that genotyping for KIR should be included in the selection process for cord blood units.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refining eligibility criteria of unit selection for myeloablative cord blood transplantation in acute leukemia: Real-world experience of a referral center. Sun, Z., Hu, Y., Ji, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03093844

Haploidentical CD34+ Selected Cells Combined With ... This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells ...

2. clinicaltrial.be clinicaltrial.be/en/details/71745?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Haploidentical CD34+ Selected Cells Combined With ... To determine the rate of successful engraftment of patients who received haploidentical CD34+ selected cells combined with single unit umbilical ...

3. withpower.com withpower.com/trial/phase-hematologic-diseases-9-2017-9c176

Haploidentical Transplant for Blood Disorders This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells ...

4. cms.gov cms.gov/medicare/coverage/ide/approved-ide-studies-items/bb17240-nct03093844

Haploidentical CD34+ Selected Cells Combined With ... Study Title. Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant for Treatment of High-risk Hematologic Disorders.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-01145

Haploidentical Stem Cell Selection using Miltenyi ... This phase I/II trial studies the side effects and how well haploidentical stem cells selected using Miltenyi CliniMACS CD34 reagent system works in ...

6. miltenyibiotec.com miltenyibiotec.com/US-en/products/clinimacs-cd34-reagent-system.html

CliniMACS® CD34 Reagent System | Miltenyi Biotec | USA The CliniMACS CD34 Reagent System is a medical device system that is designed for the in vitro enrichment of CD34 + target cells from heterogeneous hematologic ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/17/NCT01200017/Prot_000.pdf

A Phase II Study Using the CliniMACS® Device for CD34+ ... CliniMACS® CD34+ Reagent System has the advantages of the best T cell depletion efficiency achievable and a very high efficiency of CD34+ cell recovery so that ...

8. 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.