Chemotherapy + Ponatinib + Blinatumomab for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Infection, Hepatitis B, Pancreatitis, Alcohol abuse, Cardiovascular disease, 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: Unknown

Duration: Up to 15 cycles (approximately 15 months)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining low-intensity chemotherapy, ponatinib (a targeted therapy), and blinatumomab (also known as Blincyto, an immunotherapy) in treating acute lymphoblastic leukemia (ALL), especially when it has recurred or resisted treatment. These drugs work in various ways to halt cancer growth by killing cancer cells, stopping their division, or preventing their spread. The study seeks participants with Philadelphia chromosome-positive or BCR-ABL positive ALL who have faced challenges such as relapse or treatment resistance. Individuals with ALL fitting this description may be suitable for the trial. As a Phase 2 trial, this 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 does not specify if you need to stop taking your current medications, but it does mention that you cannot take strong inhibitors of CYP3A4 within at least 14 days before starting ponatinib. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that ponatinib is promising for treating certain types of leukemia. One study found it controlled chronic myeloid leukemia (CML) in 94% of patients who had relapsed or had difficult-to-treat conditions. This suggests it might also be effective for similar conditions like acute lymphoblastic leukemia (ALL). Ponatinib's safety has been carefully studied over the years, leading to improvements.

Regarding blinatumomab, research indicates it can be very effective for patients with B-cell acute lymphoblastic leukemia (B-ALL). In one study, 39% of patients treated with blinatumomab achieved complete remission, with no cancer cells found in their blood. This highlights its potential as a strong treatment option.

Both treatments have undergone various trials to ensure patient safety. While all treatments carry some risks, evidence from these studies strongly supports considering their use in clinical trials like the one described. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine traditional chemotherapy with innovative drugs like ponatinib and blinatumomab to tackle acute lymphoblastic leukemia (ALL) from multiple angles. Ponatinib is particularly notable for its ability to target specific mutations in cancer cells, potentially improving outcomes for patients who don't respond well to standard chemotherapy. Meanwhile, blinatumomab is a type of immunotherapy that helps direct the body's own immune system to attack cancer cells more effectively. This combination aims to enhance the overall treatment response and provide new hope for patients with ALL.

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

Research has shown that ponatinib effectively treats Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Studies have found that many patients respond well to ponatinib, especially when combined with chemotherapy. In this trial, participants will receive a combination of chemotherapy, ponatinib, and blinatumomab. Blinatumomab, a type of immunotherapy, has improved survival rates and helped many patients reach remission, meaning no signs of cancer. In trials, a significant number of patients remained disease-free when blinatumomab was combined with chemotherapy. Together, these treatments offer hope for those with leukemia that has returned or is resistant to other treatments. ^{1 4 5 6 7}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with Philadelphia chromosome-positive and/or BCR-ABL positive acute lymphoblastic leukemia, either untreated or resistant to treatment. Participants must be in good physical condition (ECOG <=2), have normal liver and kidney function, agree to use effective contraception, and not have a history of significant heart disease or other serious medical conditions.

Inclusion Criteria

I am 18 or older with a specific type of leukemia that has not responded to treatment.

I am 18 or older with a specific type of leukemia (Ph-positive ALL) that hasn't been treated yet.

Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome

Exclusion Criteria

I am not pregnant or breastfeeding and, if capable of becoming pregnant, will use birth control.

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

I have active hepatitis B but am on treatment to control it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity chemotherapy, ponatinib, and blinatumomab in cycles, with each cycle lasting 28 days

Up to 15 cycles (approximately 15 months)

Maintenance Therapy

Participants receive maintenance therapy with vincristine, prednisone, and ponatinib, or blinatumomab and ponatinib, depending on response

Up to 24 cycles (approximately 2 years)

Post-Maintenance Therapy

Participants receive ponatinib daily for up to 5 years in the absence of disease progression or unacceptable toxicity

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Cyclophosphamide
• Cytarabine
• Methotrexate
• Ponatinib
• Rituximab

Trial Overview The trial is testing the effectiveness of low-intensity chemotherapy combined with Ponatinib and Blinatumomab. It aims to see if this combination can stop cancer cells from growing by using different mechanisms including immune system modification.

How Is the Trial Designed?

Group I: Treatment (chemotherapy, ponatinib, blinatumomab) Experimental Treatment 9 Interventions

See Detailed Description.

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+

Published Research Related to This Trial

Blinatumomab, a bispecific T-cell engager, shows significant efficacy in treating refractory or relapsed acute lymphoblastic leukemia (ALL), achieving complete response rates of 39% to 69% and a median overall survival of 7.7 months, compared to 4.0 months with traditional chemotherapy.

The treatment has a favorable safety profile, with manageable side effects such as cytokine-release syndrome and reversible neurological issues, making it a promising option for both adult and pediatric patients with R/R ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. Queudeville, M., Handgretinger, R., Ebinger, M.[2020]

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]

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 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 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, a bispecific T-cell engager, has been successfully used in 11 pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL) after they experienced severe chemotherapy-induced toxicity, leading to recovery in all cases.

This treatment offers a nonmyelotoxic alternative for patients who cannot tolerate traditional cytotoxic therapies, suggesting it could be a valuable option in managing severe toxicity during leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia. Elitzur, S., Arad-Cohen, N., Barzilai-Birenboim, S., et al.[2020]

Blinatumomab was found to be an effective treatment for older patients (median age 75) with newly diagnosed Philadelphia chromosome-negative B-acute lymphoblastic leukemia (ALL), achieving a complete remission rate of 66%.

The 3-year disease-free survival and overall survival rates were both 37%, indicating promising outcomes for this patient population, particularly for those with poor-risk cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. Advani, AS., Moseley, A., O'Dwyer, KM., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39651791/

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic ... At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9± ...

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/PMC11164718/

Real-world evidence on treatment pattern, effectiveness, and ... Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context.

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. amgen.com amgen.com/newsroom/press-releases/2024/12/blincyto-blinatumomab-added-to-chemotherapy-significantly-improves-survival-in-newly-diagnosed-pediatric-patients-with-bcell-precursor-acute-lymphoblastic-leukemia-ball

Press Releases Phase 3 Study Results Demonstrated Three Year, Disease-Free Survival of 96%. THOUSAND OAKS, Calif. , Dec. 7, 2024 /PRNewswire/ -- Amgen ...