Combination Chemotherapy + Immunotherapy for Acute Lymphoblastic Leukemia

Overseen By Elias Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Active infection, Pancreatitis, Alcohol abuse, Cardiovascular disease, CNS pathology, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 30 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that treatment with any investigational antileukemic or chemotherapy agents should not have occurred within 2 weeks prior to study entry, unless you have fully recovered from side effects or have rapidly progressive disease.

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

Research shows that Blinatumomab improves survival in patients with relapsed or refractory acute lymphoblastic leukemia, with a median overall survival of 7.7 months compared to 4.0 months with traditional chemotherapy. It also enhances quality of life and is more cost-effective than standard chemotherapy. ^{1 2 3 4 5}

Is the combination of chemotherapy and immunotherapy for acute lymphoblastic leukemia safe?

Blinatumomab, a part of this treatment, has shown promising results in treating acute lymphoblastic leukemia with a generally favorable safety profile, though it can cause immune-related side effects like cytokine release syndrome (a severe immune reaction). Most patients tolerate it well, but it requires careful management by healthcare professionals. ^{2 6 7 8 9}

How is the drug combination of Blinatumomab, Cytarabine, Methotrexate, and Ponatinib unique for treating acute lymphoblastic leukemia?

This drug combination is unique because it includes Blinatumomab, an innovative immunotherapy that engages T-cells to attack cancer cells, offering a new approach compared to traditional chemotherapy, which often has severe side effects. Blinatumomab has shown promising results in reducing disease and improving survival in relapsed or refractory cases, making it a novel option for patients who have not responded well to standard treatments. ^{2 3 4 9 10}

What is the purpose of this trial?

This phase II trial studies how well blinatumomab, methotrexate, cytarabine, and ponatinib work in treating patients with Philadelphia chromosome (Ph)-positive, or BCR-ABL positive, or acute lymphoblastic leukemia that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as methotrexate and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab, methotrexate, cytarabine, and ponatinib may work better in treating patients with acute lymphoblastic leukemia.

Research Team

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with Philadelphia chromosome-positive or BCR-ABL positive acute lymphoblastic leukemia that's relapsed or resistant to treatment. Eligible participants must have acceptable liver and pancreas function, agree to contraception if of childbearing potential, and not be pregnant. They should not have serious infections, heart failure, uncontrolled cardiovascular disease, a history of significant bleeding disorders unrelated to cancer, active secondary malignancy expected to limit survival under one year, or CNS pathology.

Inclusion Criteria

I am 18 or older with untreated Ph-positive ALL or advanced CML.

I am 18 or older with specific types of leukemia that have not responded to treatment.

I am 18 or older with specific types of leukemia.

Exclusion Criteria

I have a serious infection that isn't getting better with antibiotics.

History of alcohol abuse

I have had a significant blood clot in my veins or arteries.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive blinatumomab IV nonstop on days 1-28 of cycles 1-5, methotrexate and cytarabine intrathecally on days 1, 15, and 29 of cycles 1-4, and ponatinib orally daily. Cycles repeat every 6 weeks.

30 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

6 months

1 visit at 30 days, then every 6 months

Treatment Details

Interventions

• Blinatumomab
• Cytarabine
• Methotrexate
• Ponatinib

Trial Overview The study tests the effectiveness of blinatumomab (an immunotherapy), methotrexate and cytarabine (chemotherapy drugs), combined with ponatinib (a drug blocking enzymes needed for cell growth) in treating patients with specific types of acute lymphoblastic leukemia. It aims to see how these treatments affect the immune system and cancer cell growth.

Participant Groups

Group I: Treatment (blinatumomab, chemotherapy, ponatinib) Experimental Treatment 4 Interventions

Patients receive blinatumomab IV nonstop on days 1-28 of cycles 1-5, and methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles 1-4. Patients also receive ponatinib PO daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Blinatumomab is already approved in European Union, United States for the following indications:

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

Blinatumomab significantly improves overall survival in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), with a median survival of 7.7 months compared to 4.0 months with traditional chemotherapy.

Patients treated with blinatumomab report a higher quality of life and lower financial burden compared to those receiving standard chemotherapy, making it a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date. Hathaway, L., Sen, JM., Keng, M.[2020]

Blinatumomab represents a significant advancement in immunotherapy for relapsed or refractory acute lymphoblastic leukemia (ALL), demonstrating unprecedented efficacy by stimulating a strong T-cell response, which is a departure from traditional chemotherapy.

While blinatumomab offers promising benefits, it also presents unique immunological toxicities and complex administration requirements, necessitating careful consideration of its use compared to other emerging therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. Rogala, B., Freyer, CW., Ontiveros, EP., 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]

Blinatumomab, a bispecific T-cell-engaging antibody, has shown a response rate of 34% to 66% in heavily pretreated children with relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), making it a promising treatment option, especially as a bridge to stem cell transplantation.

Recent randomized controlled trials indicate that blinatumomab leads to a greater reduction in minimal residual disease and improved survival compared to standard treatments, suggesting its potential for frontline use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). Queudeville, M., Ebinger, M.[2021]

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 monotherapy demonstrated a complete remission (CR) rate of 54% and a minimal residual disease (MRD) response rate of 43% in treating relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL) across 18 studies involving 1,373 patients.

The treatment showed a manageable safety profile, with 80% of patients experiencing grade ≥3 adverse events, but only 7% experiencing significant neurological toxicity and 3% experiencing cytokine release syndrome, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis. Liu, H., Xi, R., Mao, D., et al.[2023]

Blinatumomab is a promising new treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, showing effectiveness in targeting and destroying tumor cells by engaging both T-cells and B-cells.

While there are potential side effects like immunological toxicities and cytokine release syndrome, most patients tolerate blinatumomab well, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Lee, KJ., Chow, V., Weissman, A., et al.[2022]

Blinatumomab is a first-in-class bispecific T-cell engager that effectively targets both CD19 on B-cells and CD3 on T-cells, showing a high response rate of 43% for complete remission in patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-ALL).

Patients treated with blinatumomab had a median overall survival of 6.1 months and 60% achieved minimal residual disease negativity, although common side effects included fever, neurological events, and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. Buie, LW., Pecoraro, JJ., Horvat, TZ., et al.[2018]

In a phase 3 clinical trial involving 669 patients aged 1 to 30 years with first relapse of B-cell acute lymphoblastic leukemia (B-ALL), substituting blinatumomab for intensive chemotherapy in consolidation therapy showed a 2-year disease-free survival rate of 54.4% compared to 39.0% for the chemotherapy group, suggesting a potential benefit of blinatumomab in this high-risk population.

Blinatumomab also demonstrated a better safety profile, with significantly lower rates of serious adverse events such as infections and febrile neutropenia compared to traditional chemotherapy, indicating it may be a safer option for treating relapsed B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. Brown, PA., Ji, L., Xu, X., et al.[2021]

In a study involving 255 patients aged 1-30 with low-risk first relapse of B-cell acute lymphoblastic leukemia (B-ALL), blinatumomab combined with chemotherapy showed a significant improvement in disease-free survival (DFS) and overall survival (OS) for patients with bone marrow and extramedullary relapses compared to chemotherapy alone.

Blinatumomab was well tolerated with low adverse event rates, but no significant difference in outcomes was found for patients with isolated extramedullary relapses, indicating a need for new treatment strategies for this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. Hogan, LE., Brown, PA., Ji, L., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date. [2020]

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

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). [2021]

5. 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]

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

Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. [2022]

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

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. [2018]

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

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. [2021]

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

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. [2023]