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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of chemotherapy and immunotherapy treatments to evaluate their effectiveness against acute lymphoblastic leukemia (ALL), particularly when the cancer returns or resists treatment. The trial includes blinatumomab (Blincyto), which aids the immune system in fighting cancer, alongside chemotherapy drugs like methotrexate and cytarabine, and ponatinib, which inhibits cancer cell growth. Individuals with Philadelphia chromosome-positive ALL or BCR-ABL positive ALL that has recurred or is unresponsive to existing treatments may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that blinatumomab is usually well-tolerated. In one study, serious side effects occurred in about 12.5% of patients, indicating that most manage it well in real-world settings.

Cytarabine, particularly in its liposomal form, is also considered safe. A study found it safe and effective for many patients when administered after chemotherapy.

Methotrexate can cause serious liver problems, but it has effectively treated certain types of leukemia when used carefully.

Ponatinib has been used for several years, and its safety has improved over time. Some common side effects include skin and stomach issues, but many patients handle it well.

Overall, these treatments have been studied and used in various settings, demonstrating an acceptable safety profile. However, discussing potential risks with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for acute lymphoblastic leukemia, which often rely on standalone chemotherapy or immunotherapy, this combination therapy stands out by integrating both approaches. Blinatumomab, a key component, is a type of immunotherapy that uniquely targets specific proteins on cancer cells, helping the immune system to attack them more effectively. Meanwhile, ponatinib is included for its ability to inhibit certain cancer-driving enzymes, providing a multi-pronged attack alongside traditional chemotherapy agents like cytarabine and methotrexate. Researchers are excited because this blend of therapies could enhance treatment effectiveness and potentially improve patient outcomes by attacking the leukemia cells from multiple angles.

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

Research has shown that blinatumomab works well for patients with acute lymphoblastic leukemia, especially those with minimal residual disease, with 78% of patients having no detectable cancer cells after one treatment cycle. In this trial, participants will receive a combination of blinatumomab, methotrexate, cytarabine, and ponatinib. Cytarabine achieved a complete remission rate of 74% after two treatment cycles, significantly reducing leukemia cells. Methotrexate has helped patients live longer without cancer recurrence, particularly in children with leukemia. Ponatinib has been successful in treating Philadelphia chromosome-positive leukemia, with high survival rates. These treatments, when combined in this trial, attack cancer cells in different ways, increasing the chances of success. ^{1 4 6 7 8}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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, 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 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]

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 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]

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

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38662275/

Real-world evidence on treatment pattern, effectiveness ... The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re- ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3946/537699/Blinatumomab-use-in-pediatric-B-ALL-where-are-we

Blinatumomab use in pediatric B-ALL: where are we now? Among 70 patients who received the recommended dosage, 27 (39%) achieved a complete remission (CR; defined as no circulating blasts or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6173178/

Impact of blinatumomab on patient outcomes in relapsed ... A majority of the events resolved, and there were no treatment-related deaths. Overall, these data showed that blinatumomab was effective in patients with MRD ...

4. aob.amegroups.org aob.amegroups.org/article/view/11031/html

Immunotherapy with blinatumomab in B-cell acute ... Overall, 78% of patients achieved MRD negativity after one cycle of blinatumomab (18). TOWER (NCT02013167), a phase III study, further explored ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/childhood-leukemia-blincyto-first-treatment

Blincyto Effective as Initial Treatment for Childhood ALL - NCI Children in the trial treated with the combination of blinatumomab and a standard chemotherapy regimen had a substantial improvement in disease-free survival.

6. blincytohcp.com blincytohcp.com/clinical-data/adult-aya/real-world-evidence-study

Real-World Evidence in Adult & AYA B-cell ALL See real-world clinical outcomes for BLINCYTO® (blinatumomab) in treating adult and AYA patients with B-cell acute lymphoblastic leukemia (ALL).

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119413098

Safety and Efficacy of Blinatumomab- Real World Data Despite improvement in survival of newly diagnosed adult ALL, the results of relapsed/refractory disease are still poor, with long term survival of < 10%.

8. nature.com nature.com/articles/s41408-024-01179-4

Frontline Ph-negative B-cell precursor acute lymphoblastic ... Additionally, 3-year relapse-free survival was 80% for the blinatumomab arm versus 64% for chemotherapy alone (HR, 0.53 [95% CI, 0.32–0.87]; P = ...