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

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a study to evaluate the safety and efficacy of Miltenyi CliniMACS® CD34 Reagent System to promote engraftment of haploidentical CD34+ selected cells combined with single unit umbilical cord blood transplant for treatment of high-risk hematologic disorders.

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 safety data is available for haploidentical transplants for blood disorders?

The safety data for haploidentical transplants, including those using CD34+ selected cells combined with umbilical cord blood, indicates that this approach can result in rapid engraftment with no increased rate of graft failure or graft-versus-host disease (GVHD). In a study of 26 patients, the incidence of grade 2-4 acute GVHD was 27% at day +100, and chronic GVHD was 4% at 1 year. Overall survival at 1 year was 54%. Recent advances have reduced historical issues of graft rejection and severe GVHD, making haploidentical stem cell transplantation a viable option for patients without a fully matched donor. However, post-transplant infectious complications and relapse remain challenges. ^{1 2 3 4 5}

Is haploidentical transplant generally safe for humans?

Haploidentical transplants, which use a partially matched family donor, have shown promising safety results. Studies indicate that recent advances have reduced issues like graft rejection and severe graft-versus-host disease (a condition where the donor's immune cells attack the recipient's body), making it a viable option for those without fully matched donors. ^{1 2 3 6 7}

Is the treatment Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant a promising treatment for blood disorders?

Yes, this treatment is promising because it provides an alternative for patients who don't have a fully matched donor. It allows for nearly immediate donor availability and has shown improved outcomes over the past decade. This approach helps meet the need for stem cell transplants, especially for those with diverse backgrounds or urgent needs. ^{6 8 9 10 11}

How is the treatment Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant different from other treatments for blood disorders?

This treatment is unique because it combines haploidentical stem cells, which are partially matched from a family member, with umbilical cord blood cells, allowing for a broader range of donor options and potentially faster availability. It addresses the challenge of finding fully matched donors and aims to improve outcomes by using both sources to enhance engraftment and immune recovery. ^{6 8 9 10 11}

What data supports the idea that Haploidentical Transplant for Blood Disorders is an effective treatment?

The available research shows that Haploidentical Transplant for Blood Disorders, when combined with umbilical cord blood, can lead to successful outcomes. In one study, 83% of patients experienced successful engraftment, which means the transplanted cells started to grow and produce healthy blood cells. Additionally, the study reported a 54% overall survival rate at one year, indicating that more than half of the patients were still alive after a year. This suggests that the treatment can be effective for patients who do not have a fully matched donor. Compared to other methods, such as using two mismatched cord blood units, this approach provides a viable alternative with rapid recovery of blood cells and a lower risk of complications like graft-versus-host disease, where the new immune cells attack the patient's body. ^{1 7 12 13 14}

What data supports the effectiveness of the treatment Haploidentical CD34+ Selected Cells Combined With Single Unit Umbilical Cord Blood Transplant?

Research shows that using a combination of haploidentical CD34+ selected cells and umbilical cord blood can lead to rapid recovery of blood cells and a good chance of successful engraftment, with 83% of patients achieving this by day 60. This approach also has a relatively low incidence of severe graft-versus-host disease, a common complication in transplants. ^{1 7 12 13 14}

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

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]

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 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]

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]

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]

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 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]

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]

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 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]

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]

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 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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Cord blood transplants supported by unrelated donor CD34+ progenitor cells. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Double-chimaerism after transplantation of two human leucocyte antigen mismatched, unrelated cord blood units. [2019]

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

Human Multi-Chimeric Cell (HMCC) Therapy as a Novel Approach for Tolerance Induction in Transplantation. [2023]

4. United States 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. [2023]

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

Double umbilical cord blood transplantation: relevance of persistent mixed-unit chimerism. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. [2019]

7. England pubmed.ncbi.nlm.nih.gov

The role of haploidentical stem cell transplantation in the management of children with haematological disorders. [2019]

8. China pubmed.ncbi.nlm.nih.gov

[Treatment of two case childhood acute lymphoblastic leukemia by HLA-mismatched unrelated umbilical cord blood transplantation]. [2016]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Alternate Donor Transplantation. [2023]

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

Haploidentical bone marrow transplantation in Mexico. [2012]

12. Turkey pubmed.ncbi.nlm.nih.gov

Strategies in haploidentical stem cell transplantation in adults. [2021]

13. England pubmed.ncbi.nlm.nih.gov

The great debate: haploidentical or cord blood transplant. [2011]

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

Overview of the progress on haploidentical hematopoietic transplantation. [2020]