Stem Cell Transplant for Blood Cancers

(AB-CliniMACs Trial)

Overseen By Megan Atkinson

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: No suitable donor, Previous transplant, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 11 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell transplant method for individuals with certain blood cancers. Researchers aim to determine if stem cells from donors who are not close family matches can be effective and safe. The study focuses on preventing complications such as graft versus host disease, where donor cells attack the patient's body, and on improving survival rates. Participants should have a blood cancer like leukemia or lymphoma that is currently under control and must not have any active infections. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

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.

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

Research has shown that using a special type of stem cell transplant, which removes certain T cells, can be safe and effective. This method helps prevent graft versus host disease (GVHD), a serious issue where new cells attack the body. It is used in children and young adults with blood cancers and is considered safe.

Another study found that patients who received stem cells with both specific T cells and B cells removed experienced positive results. The treatment proved to be safe and manageable, with few complications.

While these studies provide promising safety data, the current trial remains in a phase where researchers are still learning about the treatment's effects. They continue to gather information to ensure its safety for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore innovative ways to enhance stem cell transplants for blood cancers. Unlike traditional methods, which often rely on chemotherapy and radiation, these experimental treatments use alpha beta T cell depletion strategies with or without total body irradiation. This approach aims to reduce the risk of transplant-related complications, like graft-versus-host disease, by depleting specific immune cells. Additionally, the use of different conditioning regimens, such as non-irradiation and varied sequences of irradiation, could optimize patient outcomes by tailoring the treatment to individual needs. By investigating these diverse protocols, researchers hope to improve the safety and effectiveness of stem cell transplants in treating blood cancers.

What evidence suggests that this trial's treatments could be effective for blood cancers?

This trial will evaluate different approaches to stem cell transplants for blood cancers, specifically focusing on alpha beta T cell depletion. Studies have shown that removing certain T cells from stem cell transplants can effectively treat blood cancers. This method also involves removing specific B cells to reduce the risk of graft versus host disease (GVHD), a common complication. Research indicates that this approach helps new cells grow well in the patient's body. It is considered a safe and effective option, especially for patients receiving transplants from partially matched donors. Initial findings suggest that patients receiving this type of transplant have better chances of remaining leukemia-free. ^{2 3 4 6 7}

Who Is on the Research Team?

Timothy S Olson, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for patients with various blood cancers like leukemia and lymphoma who are in remission or have minimal disease presence. They must have acceptable organ function, no active untreated infections, and a negative pregnancy test if applicable. Those who've had previous allogeneic transplants or lack a suitable donor can't participate.

Inclusion Criteria

My leukemia/lymphoma is in remission or has less than 10% bone marrow blasts.

I am not pregnant.

Signed informed consent

Exclusion Criteria

No suitable donor

I have had a transplant from a donor who is not my sibling.

My condition does not match the specific disease, organ, or infection criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive α/β T cell-depleted peripheral Stem Cell Transplantation with various conditioning regimens including TBI, Busulfan, Thiotepa, and Cyclophosphamide

11 days

Follow-up

Participants are monitored for engraftment, graft versus host disease (GVHD), and leukemia-free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Stem Cell Transplant
• Alpha Beta T cell depletion

Trial Overview The study tests α/β T cell-depleted peripheral Stem Cell Transplantation using alternative donors to treat blood cancers. It aims to see how well patients accept the transplant without developing graft versus host disease (GVHD) and their survival rate without leukemia after one year.

How Is the Trial Designed?

Group I: Alpha Beta Total Body Irradiation - total body irradiation (TBI) first Experimental Treatment 1 Intervention

Alpha Beta Total Body Irradiation - TBI first Day Treatment * 11 Anti-thymocyte globulin (ATG) * 10 ATG * 9 ATG * 8 TBI * 7 TBI * 6 TBI * 5 Thiotepa * 4 Thiotepa * 3 Cyclophosphamide * 2 Cyclophosphamide * 1 Rest 0 Transplant with alpha beta T cell depleted stem cells

Group II: Alpha Beta Total Body Irradiation - TBI last Experimental Treatment 1 Intervention

Alpha Beta Total Body Irradiation - TBI last Day Treatment * 9 ATG * 8 ATG * 7 Thiotepa + ATG * 6 Thiotepa * 5 Cyclophosphamide * 4 Cyclophosphamide * 3 TBI * 2 TBI * 1 TBI 0 Transplant with alpha beta T cell depleted stem cells

Group III: Alpha Beta Non-irradiation regimen Experimental Treatment 1 Intervention

Alpha Beta Non-irradiation regimen Day Treatment * 9 Busulfan + ATG * 8 Busulfan + ATG * 7 Busulfan +ATG * 6 Busulfan * 5 Thiotepa * 4 Thiotepa * 3 Cyclophosphamide * 2 Cyclophosphamide * 1 0 Transplant with alpha beta T cell depleted stem cells

Allogeneic Stem Cell Transplant is already approved in United States, European Union for the following indications:

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Approved in European Union as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

In a study of 206 patients who underwent unrelated haematopoietic stem cell transplantation (HSCT), those receiving HLA-identical grafts had similar overall survival rates (52%) compared to those with one or more mismatched antigens (48%) after a median follow-up of 49 months.

The findings suggest that using donors with one antigen mismatch is a viable option for patients with hematological malignancies when fully matched donors are not available, as outcomes in terms of survival and graft-versus-host disease were comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable outcome after single-antigen-mismatched versus matched unrelated donor haematopoietic cell transplantation. Rockstroh, A., Al-Ali, HK., Lange, T., et al.[2018]

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) with sibling donors experience a complex mix of emotions, feeling both secure in their donor's support and burdened by a sense of responsibility for the donor's safety.

The study highlights the need for healthcare providers to understand the emotional challenges faced by patients and their sibling donors, as this can impact their care and overall experience during the transplantation process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Having a sibling as donor: patients' experiences immediately before allogeneic hematopoietic stem cell transplantation. Kisch, A., Bolmsjö, I., Lenhoff, S., et al.[2022]

Long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) show significantly reduced left ventricular (LV) systolic function compared to healthy controls, with 44.2% experiencing left ventricular systolic dysfunction (LVSD).

Factors such as age, previous treatment with anthracyclines, graft versus host disease (GVHD), heart rate, and hypertension are independently associated with decreased LV function, indicating the need for ongoing cardiac monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation. Massey, RJ., Diep, PP., Ruud, E., et al.[2022]

In a small study of four patients with metastatic colorectal cancer who underwent reduced-intensity stem-cell transplantation (RIST), all patients tolerated the treatment well and showed signs of a graft-versus-tumor effect, indicating potential efficacy against the cancer.

Despite experiencing acute or chronic graft-versus-host disease (GvHD), three patients had stable disease or partial response after RIST, suggesting that allo-SCT may be a promising approach for treating colorectal cancer, warranting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-intensity allogeneic hematopoietic stem-cell transplantation as an immunotherapy for metastatic colorectal cancer. Kojima, R., Kami, M., Hori, A., et al.[2019]

In a study of 34 high-risk patients undergoing allogeneic blood stem cell transplantation with a minimal intensive conditioning regimen, 94% achieved successful engraftment of donor cells, indicating a high efficacy of the treatment.

The approach resulted in a 65% survival rate after a median follow-up of 325 days, with significant clinical responses observed in 59% of patients with active disease at the time of transplantation, suggesting improved safety and outcomes compared to conventional transplantation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliable engraftment, low toxicity, and durable remissions following allogeneic blood stem cell transplantation with minimal conditioning. Kobbe, G., Schneider, P., Aivado, M., et al.[2019]

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critical treatment option for various diseases, but it carries risks of morbidity and mortality, highlighting the importance of donor safety during the stem cell donation process.

Bone marrow donation is a well-established and generally safe procedure, with a low incidence of serious adverse events (only 1 fatal event reported among 27,770 donations), and the most common side effects being pain and fatigue, indicating that careful donor selection is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of bone marrow stem cell donation: a review. Bosi, A., Bartolozzi, B.[2010]

Allogeneic hematopoietic stem cell transplantation is an effective curative treatment for various blood cancers, leveraging the immune response from donor cells to fight tumors, known as the 'graft versus leukemia' effect.

Despite advancements in reducing short-term toxicity and managing complications, graft versus host disease remains a significant challenge, leading to prolonged immunosuppression and increased risk of infections, yet the procedure continues to expand due to its demonstrated efficacy against both myeloid and lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic hematopoietic stem cell transplantation]. Mohty, M.[2009]

Hematopoietic stem cell transplantation (HSCT) has evolved significantly over the past 45 years, with autologous HSCT primarily used after high-dose chemotherapy and allogeneic HSCT utilized for treating marrow failures and enhancing anti-tumor effects.

In 2010, approximately 30,000 patients underwent HSCT in Europe, and recent advancements in patient and donor selection, stem cell sourcing, and supportive care have expanded the indications for allogeneic HSCT, improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation: a review and recommendations for follow-up care for the general practitioner. Passweg, JR., Halter, J., Bucher, C., et al.[2018]

Allogeneic hematopoietic stem cell transplantation (HSCT) can potentially replace a diseased immune system with healthy donor cells, showing promise in treating conditions like severe aplastic anemia and autoimmune diseases, but results can vary widely with both complete remissions and treatment failures reported.

Despite its potential benefits, allogeneic HSCT is associated with significant risks, including morbidity and mortality, leading to the conclusion that it cannot be generally recommended without further carefully conducted studies to identify the best patient populations and treatment technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. Gratwohl, A.[2009]

In a study of 401 patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) for advanced hematological diseases, the 5-year overall survival (OS) rate was 27.3% and disease-free survival (DFS) was 21.1%.

The analysis revealed that the type of underlying malignancy significantly affected both OS and DFS, while the development of severe acute graft versus host disease (GvHD) negatively impacted OS; interestingly, chronic GvHD was associated with better outcomes, highlighting the importance of immunological responses in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic graft versus host disease but not the intensity of conditioning has impact on survival after allogeneic hematopoietic stem cell transplantation for advanced hematological diseases. Hilgendorf, I., Wolff, D., Nogai, A., et al.[2014]

In a study of 103 long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT), nearly half exhibited pathological findings on high-resolution CT scans, indicating significant pulmonary complications, including chronic graft-versus-host disease in 33% of participants.

Survivors showed lower pulmonary function compared to healthy controls, with mean lung volumes over 80% of predicted values, highlighting the need for lifelong monitoring of pulmonary health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-Onset, Noninfectious Pulmonary Complications following Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Cohort Study of Long-Term Survivors. Myrdal, OH., Aaløkken, TM., Diep, PP., et al.[2022]

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is becoming more effective with the use of unrelated donors and cord blood grafts, achieving results comparable to sibling donor transplants.

New strategies like reduced-intensity conditioning for older patients and the use of donor lymphocyte infusions (DLIs) show promise in improving outcomes, including anti-tumor effects against solid tumors and better management of disease relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation: current status and future outlook. Aschan, J.[2019]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a powerful curative option for patients with specific blood disorders, showing significant advancements in recent years.

Key improvements include the use of haploidentical HSCT and enhanced strategies for managing aplastic anemia, relapse, and graft versus host disease, particularly in the context of practices in China.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allo-Hematopoietic Stem Cell Transplant in China: 2014 Update. Lv, M., Huang, XJ.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05800210

NCT05800210 | Alpha/Beta T Cell and CD19+ B ... This study will assess the safety, efficacy, and feasibility of ⍺/β CD3+ T-cell and CD19+ B-cell depletion in allogeneic stem cell transplantation in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34872106/

Unrelated donor α/β T cell- and B cell-depleted HSCT for the ... Outcome data with TCRαβ/CD19 depletion generally describe haploidentical donors, with relatively few URDs. We hypothesized that TCRαβ/CD19- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02323867

Allogeneic Stem Cell Transplant With Alpha/Beta T AND B ... This is a single arm pilot study for patients using α/β T cell-depleted peripheral Stem Cell Transplantation (PSCT) in with alternative donor sources with ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0966327425000486

Comprehensive up-to-date analysis on TCRαβ/CD19 ... This meta-analysis assesses the efficacy of TCRαβ+/CD19+ depleted hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological ...

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Unrelated donor α/β T cell– and B cell–depleted HSCT for ... URD HSCT with TCRαβ/CD19 depletion is a safe and effective approach to alternative donor transplantation for hematologic malignancies.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05735717

MT2021-08T Cell Receptor Alpha/Beta Depletion PBSC ... This is a phase II, open-label, prospective study of T cell receptor alpha/beta depletion peripheral blood stem cell (PBSC) transplantation for children and ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05517

T Cell Receptor Alpha/Beta Depletion Peripheral Blood ... This phase II trial tests how well T cell receptor Alpha/Beta depletion (A/B TCD) peripheral blood stem cell transplantation works to prevent graft versus host ...