Blinatumomab + Ponatinib for Acute Lymphoblastic Leukemia

JB
Overseen ByJoseph Brandwein, MD, FRCPC
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: University of Alberta
Must be taking: Ponatinib, Prednisone
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, blinatumomab and ponatinib, for treating B-cell acute lymphoblastic leukemia (B-ALL) with a specific mutation known as BCR-ABL. Blinatumomab, a type of immunotherapy, helps the immune system attack cancer cells and is administered under the skin, while ponatinib is a pill that targets the mutation. The trial aims to evaluate the effectiveness of this combination and identify potential side effects. Individuals with BCR-ABL positive B-ALL, who have not yet received full treatment and have more than 5% leukemia cells in their bone marrow, might be suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific situation with the trial team or your doctor.

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

Research has shown that combining blinatumomab and ponatinib is generally safe for treating B-cell acute lymphoblastic leukemia (B-ALL). In one study, only about 16% of patients experienced mild to moderate side effects, indicating most tolerated the treatment well. Another study found that 90% of patients survived for at least four years after treatment, demonstrating the treatment's effectiveness and reasonable safety. Although all treatments can cause side effects, the low rate of negative reactions is encouraging for this combination.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of blinatumomab and ponatinib for treating acute lymphoblastic leukemia because it offers a novel approach compared to standard chemotherapy and tyrosine kinase inhibitors. Blinatumomab is a bispecific T-cell engager that uniquely recruits the body’s own immune cells to target and destroy cancer cells, offering a different mechanism of action than traditional treatments. Additionally, ponatinib is a potent inhibitor of a broad spectrum of BCR-ABL mutations, including those resistant to other therapies, potentially addressing a gap in current treatment options. Together, these drugs may offer a more targeted and effective treatment approach for patients who don't respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for B-ALL?

This trial will evaluate the combination of blinatumomab and ponatinib for treating B-cell acute lymphoblastic leukemia (B-ALL) with the BCR-ABL mutation. Research has shown that using blinatumomab and ponatinib together is promising. In one study, patients who received these drugs had a 4-year survival rate of about 90%. Another study found that this combination led to an overall survival rate of 94%, which surpasses some traditional treatments. Blinatumomab helps the immune system find and destroy leukemia cells, while ponatinib targets the BCR-ABL mutation in these cells. These results suggest that this drug combination could effectively treat this aggressive type of leukemia.1678

Are You a Good Fit for This Trial?

This trial is for adults with a type of aggressive blood cancer called B-ALL that has the BCR-ABL mutation. Participants should be able to take medication orally and receive injections under the skin.

Inclusion Criteria

I haven't had initial treatment for ALL, except short-term steroids or hydroxyurea.
My leukemia is Ph positive and CD19 positive.
Greater than or equal to 5% blasts in the BM
See 3 more

Exclusion Criteria

I have had significant heart problems in the last 3 months.
Subject considered unsuitable for study for any other reason in the physician's best judgement
I do not have any infections that aren't responding to treatment.
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive ponatinib 30 mg/day for 70 days, with prednisone for the first month

10 weeks
Regular visits for blood and bone marrow tests

Consolidation

Participants receive 5 cycles of blinatumomab injections and ponatinib, with a 2-week break between cycles

20 weeks
3 visits per week for blinatumomab injections

Maintenance

Participants continue ponatinib tablets alone for 5 years from the start of treatment

5 years
Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Blinatumomab

Trial Overview

The trial tests subcutaneous blinatumomab combined with oral ponatinib tablets in treating BCR-ABL positive B-ALL. It involves initial treatment with ponatinib, followed by repeated cycles of blinatumomab injections and continuous ponatinib intake over five years.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Treatment with subcutaneous blinatumomab plus ponatinibExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials
957
Recruited
437,000+

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
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Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

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Paul Burton

Amgen

Chief Medical Officer since 2023

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

Citations

Results of the Simultaneous Combination of Ponatinib and ...

The Hyper-CVAD and ponatinib regimen further improved the 5-year OS to 75% while reducing the need for HSCT. Blinatumomab was highly active in refractory- ...

Blinatumomab and ponatinib demonstrates ongoing efficacy ...

Blinatumomab and ponatinib demonstrates ongoing efficacy as frontline therapy in Philadelphia positive B-cell acute lymphoblastic leukemia: Long ...

Blinatumomab and ponatinib vs. hyper-CVAD and ...

Blinatumomab and ponatinib have been shown to be highly effective with a 4-year survival rate around 90%. However, there is no randomized trial ...

Blinatumomab/Ponatinib Provides Chemo-Free Option in ...

The overall survival (OS) was 94% (range, 91%-98%) in the ponatinib plus blinatumomab arm vs 77% (range, 66%-91%) in the control arm, and 97% ( ...

Efficacy and safety of combination therapy of ponatinib and ...

Additionally, the incidence of grade 1–4 adverse events remained low, at 16% (95% CI: 0.055–0.282; I² = 77.51%; P = 0.004). In contrast, the ...

Blinatumomab and ponatinib vs. hyper-CVAD and ponatinib in ...

Blinatumomab and ponatinib have been shown to be highly effective with a 4-year survival rate around 90%. However, there is no randomized trial ...

0052 Efficacy and safety of combination therapy ...

This analysis suggests ponatinib and blinatumomab can achieve improved survival, molecular responses, and low relapse rates within 24 months with manageable ...

Acute Lymphoblastic Leukemia ALL-424 Updated Results ...

Conclusions: The chemotherapy-free combination of blinatumomab and ponatinib demonstrated robust clinical activity in Ph-positive ALL, with high rates of CMR ...