Blinatumomab + HCT for Acute Lymphoblastic Leukemia

Overseen By Meredith Beversdorf, RN

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Chemotherapy, Radiation, Immunotherapy, others

Disqualifiers: Active infection, Pregnancy, Active malignancy, 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: 19

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat high-risk B cell acute lymphoblastic leukemia (ALL), aiming to reduce relapse and improve survival. It combines a special type of bone marrow transplant, known as hematopoietic cell transplantation (HCT), with a follow-up medication called blinatumomab. The trial consists of two parts, varying in treatment intensity based on specific leukemia markers. Suitable participants have high-risk B-ALL, are in remission, and have an unrelated or partially matched donor available for the transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot receive other chemotherapy, radiation, or immunotherapy while participating. If you are on transplant immune suppression therapy, you must stop it at least 7 days before joining the trial.

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

Research shows that blinatumomab, when used alone, effectively treats relapsed B-cell acute lymphoblastic leukemia (ALL) in adults. This treatment aids the immune system in fighting leukemia. Most patients tolerate it well, though some experience side effects like fever and headaches.

Studies have examined a special type of stem cell transplant, called alpha/beta T-cell and B-cell depleted hematopoietic cell transplantation (HCT), in children and young adults with leukemia. Research indicates that this transplant method is safe and effective, with a strong record in managing leukemia.

The researchers are exploring the combination of these treatments—using blinatumomab after the specialized HCT—to reduce risks and improve outcomes. The trial is in an early phase, and safety data is still being collected, but previous studies suggest it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute lymphoblastic leukemia because they combine advanced transplant techniques with a targeted immunotherapy. Unlike standard treatments that often rely on chemotherapy, this approach uses a specially prepared stem cell transplant that depletes specific T-cells and B-cells, potentially reducing the risk of complications. Additionally, blinatumomab, a type of immunotherapy, is delivered as a continuous infusion post-transplant, aiming to target and eliminate any remaining cancer cells with precision. This combination could offer a more tailored and less toxic alternative to traditional methods, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

This trial will evaluate two different treatment approaches for acute lymphoblastic leukemia. One arm involves a special type of stem cell transplant that removes certain T-cells and B-cells, followed by a myeloablative conditioning regimen. Research has shown that this type of transplant is a promising way to treat leukemia, with quick recovery of T-cells linked to better results in children with leukemia.

The other arm involves a reduced intensity conditioning regimen followed by the same type of transplant. Both arms will include a 28-day continuous infusion of blinatumomab starting on Day 100 post-transplant. Research has shown that blinatumomab helps patients with B-cell acute lymphoblastic leukemia (ALL) live without the disease. In one study, 78% of patients had no detectable cancer cells after treatment. Another study found that when blinatumomab was used with chemotherapy, 96% of patients were disease-free after three years. These treatments together show promise for improving outcomes in high-risk B-cell ALL. ^{1 6 7 8 9}

Who Is on the Research Team?

Rachel Phelan, MD, MPH

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for young people (≤25 years) with high-risk B-cell acute lymphoblastic leukemia. They must be in remission or have very-high risk biology ALL and an available donor for a stem cell transplant. Participants need good organ function, controlled seizures if present, no active infections or GVHD, and agree to use contraception.

Inclusion Criteria

My B-ALL is in remission with no detectable disease in my bone marrow.

Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

I can care for myself but may not be able to do active work or play.

Exclusion Criteria

Participating in a concomitant Phase 1 or 2 study involving treatment of disease.

I have an active cancer that is not B-cell Acute Lymphoblastic Leukemia.

I am not pregnant or breastfeeding and have taken a pregnancy test within the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants receive either a myeloablative or reduced intensity conditioning regimen followed by an alpha/beta T-cell and B-cell depleted transplant

4-6 weeks

Blinatumomab Therapy

Participants receive a 28-day continuous infusion of blinatumomab starting on Day 100 post-transplant

4 weeks

Continuous infusion

Follow-up

Participants are monitored for safety, effectiveness, and various outcomes such as cytokine analysis and lymphocyte function

1 year

Multiple visits at Days +19, +91, +135, +180, and 1 year post-HCT

What Are the Treatments Tested in This Trial?

Interventions

• Alpha/Beta T-cell and B-cell depleted HCT
• Blinatumomab

Trial Overview The study tests alpha/beta T-cell and B-cell depleted hematopoietic cell transplantation followed by blinatumomab therapy to see if it can lower relapse rates and improve survival in patients with high-risk B-ALL while reducing treatment side effects.

How Is the Trial Designed?

Group I: Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT Experimental Treatment 2 Interventions

Patients who are MRD Negative by Flow cytometry and are MRD Negative by High Throughput Sequencing, will receive a reduced intensity conditioning regimen followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.

Group II: Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT Experimental Treatment 2 Interventions

Patients who are MRD Negative by Flow cytometry but are MRD Positive by High Throughput Sequencing, will receive a myeloablative conditioning regimen which includes total body irradiation (TBI) followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.

Alpha/Beta T-cell and B-cell depleted HCT is already approved in United States, European Union for the following indications:

Approved in United States as Blincyto for:

• B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children with minimal residual disease (MRD) greater than or equal to 0.1%
• Relapsed or refractory B-cell precursor ALL

Approved in European Union as Blincyto for:

• Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
• B-cell precursor ALL in first or second complete remission with minimal residual disease greater than or equal to 0.1%

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Blinatumomab is a groundbreaking treatment for B-cell precursor relapsed/refractory acute lymphoblastic leukemia (ALL), showing the ability to induce deep remissions in some patients, but many still do not respond or relapse, highlighting the need for improved treatment strategies.

Understanding how patients respond or resist blinatumomab could help identify those who will benefit most, and combining it with other therapies or using it earlier in treatment protocols may enhance its effectiveness and reduce relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. Chitadze, G., Laqua, A., Lettau, M., et al.[2021]

Blinatumomab (Blincyto) received accelerated approval for treating B-cell precursor acute lymphoblastic leukemia (ALL) in patients with minimal residual disease, highlighting its efficacy in maintaining remission in both adults and children.

As a bispecific CD19-directed CD3 T-cell engager, blinatumomab works by activating T-cells to target and eliminate leukemia cells, demonstrating a novel mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. Mattison, RJ.[2018]

In a phase 2 study involving 23 patients with high-risk B-lineage acute lymphoblastic leukemia (ALL), administering 4 cycles of blinatumomab after allogeneic hematopoietic cell transplantation (HCT) was found to be feasible, with 57% of patients completing all cycles and a 1-year overall survival rate of 85%.

The effectiveness of blinatumomab was influenced by the patients' immune profiles, with responders showing higher levels of effector memory CD8 T-cells, while nonresponders had T-cell deficiencies and higher levels of inhibitory checkpoint molecules, indicating that the immune environment plays a crucial role in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. Gaballa, MR., Banerjee, P., Milton, DR., et al.[2023]

In a study of 197 patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, blinatumomab demonstrated a significantly higher complete remission (CR) rate of 80.8% compared to 53.8% for conventional chemotherapy, indicating its greater efficacy.

Blinatumomab also led to a lower regimen-related mortality rate (1.9% vs. 40.4%) and improved overall survival at 3 years (33.2% vs. 15.4%), highlighting its safety and effectiveness as a treatment option before allogeneic hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score-matched cohort analysis. Yoon, JH., Kwag, D., Lee, JH., et al.[2023]

Blinatumomab, a bispecific T-cell engager, has shown effectiveness in achieving negative minimal residual disease in patients with relapsed or refractory pre-B acute lymphoblastic leukemia after conventional chemotherapy.

In a case study, a patient with good health underwent successful allogenic stem cell transplantation after just one cycle of blinatumomab, suggesting its potential as an off-label treatment to enhance cytological remission before transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Blinatumomab as a bridge to trasplantation in refractory Philadelphia chromosome negative b-cell acute lymphoblastic leukemia: a case report]. Rodríguez-Ferreras, A., Zapico-García, I.[2019]

Blinatumomab therapy before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) effectively induced minimal residual disease (MRD)-negative remissions, leading to improved leukemia-free survival (LFS) compared to chemotherapy alone.

Importantly, blinatumomab did not increase the risk of post-transplant complications such as graft-versus-host disease (GVHD) or graft failure, suggesting it is a safe option for pre-HCT treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with B Cell Acute Lymphoblastic Leukemia. Llaurador, G., Shaver, K., Wu, M., et al.[2023]

In a study of 23 adults with B-cell acute lymphoblastic leukemia treated with blinatumomab, pre-emptive intravenous immune globulin (IVIG) did not reduce the incidence of hypogammaglobulinemia or associated infections compared to a control group.

Both groups experienced similar rates of infections and immunoglobulin levels, indicating that IVIG repletion may not be effective in mitigating the risks associated with blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. Wo, S., Levavi, H., Mascarenhas, J., et al.[2022]

Citations

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Very early recovery of T cells after alpha/beta T ... Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia. Author links ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8864664/

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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04746209

Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT This trial will assess the feasibility of alpha/beta T-cell and B-cell depleted allogeneic hematopoietic cell transplantation (HCT) followed by blinatumomab ...

4. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/170/481241/Alphabeta-T-and-B-Cell-Depleted-HLA-Haploidentical

Alphabeta T and B-Cell Depleted HLA-Haploidentical ... Conclusions: These data indicate that TBdepl-haploHSCT is a safe and effective transplant option also in children with MDS. Indeed, the low risk ...

5. isct-cytotherapy.org isct-cytotherapy.org/article/S1465-3249(25)00785-6/fulltext

Very early recovery of T cells after alpha/beta T ... In this retrospective study, we've focused on a homogeneous cohort of 262 children with acute leukemia first transplanted in complete remission, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25524800/

Safety and activity of blinatumomab for adult patients with ... Single-agent blinatumomab showed antileukaemia activity in adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia characterised ...

7. jhoponline.com jhoponline.com/articles/blinatumomab-a-step-forward-in-the-treatment-of-b-cell-precursor-acute-lymphoblastic-leukemia

Blinatumomab: A Step Forward in the Treatment of B-Cell ... Blinatumomab represents a novel approach to the treatment of B-cell precursor ALL (B-ALL), by activating the patient's own immune system.

8. sciencedirect.com sciencedirect.com/science/article/pii/S2473952921008430

Unrelated donor α/β T cell– and B cell–depleted HSCT for ... URD TCRαβ/CD19-depleted peripheral HSCT is a safe and effective approach to transplantation for children/YAs with leukemia.

9. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/09/NCT04746209/Prot_SAP_000.pdf

Blinatumomab After TCR αβ/CD19 Depleted HCT The experience by the Italian group led to a subsequent trial in children with acute leukemia using the same alpha/beta T cell/B cell depletion.51 Eighty ...