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

Trial Summary

What is the purpose of this trial?

This trial will assess the feasibility of alpha/beta T-cell and B-cell depleted allogeneic hematopoietic cell transplantation (HCT) followed by blinatumomab therapy for high-risk B cell acute lymphoblastic leukemia (ALL) as a means of reducing rates of subsequent relapse and improving survival, while also minimizing treatment-related morbidity/ mortality and late effects. The conditioning regimens will be dependent on the patient's minimal residual disease (MRD) status prior to HCT using high throughput sequencing.

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.

What data supports the effectiveness of the drug Blinatumomab for treating acute lymphoblastic leukemia?

Blinatumomab has shown effectiveness in achieving complete remission and minimal residual disease (MRD)-negative status in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). It has been associated with favorable outcomes when used before allogeneic hematopoietic cell transplantation (allo-HCT), leading to better survival rates compared to conventional chemotherapy. ^{1 2 3 4 5}

Is Blinatumomab + HCT safe for treating acute lymphoblastic leukemia?

Blinatumomab, used with hematopoietic cell transplantation (HCT), has shown to be generally safe in treating acute lymphoblastic leukemia, with some risks of immune-related side effects like graft-versus-host disease (GVHD) and neurotoxicity. However, these side effects are usually minimal, and the treatment is considered feasible and beneficial for many patients. ^{1 2 3 4 6}

How is the treatment with Blinatumomab and HCT different for acute lymphoblastic leukemia?

This treatment is unique because it combines Blinatumomab, a drug that helps the immune system target and destroy cancer cells, with a special type of stem cell transplant (HCT) that removes certain immune cells to reduce complications. Blinatumomab is known for its ability to help patients achieve remission when other treatments have failed, making it a promising option for those with difficult-to-treat leukemia. ^{1 3 4 5 7}

Research Team

Rachel Phelan, MD, MPH

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 (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]

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]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]

2. United States 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. [2023]

3. England 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. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

[Blinatumomab as a bridge to trasplantation in refractory Philadelphia chromosome negative b-cell acute lymphoblastic leukemia: a case report]. [2019]

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

A closer look at blinatumomab. [2018]

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

Blinatumomab maintenance after allogeneic hematopoietic cell transplantation for B-lineage acute lymphoblastic leukemia. [2023]

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

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]