Blinatumomab + Dasatinib/Imatinib for Acute Lymphoblastic Leukemia

Recruiting at 110 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Tyrosine kinase inhibitors

Must not be taking: Other TKIs

Disqualifiers: Chronic myeloid leukemia, Down syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 13

222 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs—blinatumomab (a type of immunotherapy), dasatinib, and imatinib—alongside standard chemotherapy to treat acute lymphoblastic leukemia (ALL). It targets patients with the Philadelphia chromosome or similar genetic markers, which make the cancer more aggressive. The goal is to determine if this combination more effectively stops cancer growth than current treatments. Suitable candidates have recently been diagnosed with these specific types of ALL and have already begun standard induction chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially more effective treatments.

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

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients may have started either imatinib or dasatinib before joining the study, but should not have received more than 14 days of these medications for Ph+ B-ALL or 35 days for ABL-class Ph-like B-ALL.

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

Research shows that blinatumomab is usually well-tolerated by patients with B-cell acute lymphoblastic leukemia (B-ALL). In studies, patients treated with blinatumomab had encouraging survival rates; one study reported that 80% of certain patients were relapse-free after three years. This indicates that many can undergo the treatment without major problems.

For dasatinib, research indicates it is safe, especially when combined with other treatments. In one study, most patients remained healthy and disease-free after using dasatinib with blinatumomab. Some side effects can occur, but they are generally manageable with proper care.

Imatinib, another treatment option in the trial, has been tested in various situations. While some patients experienced significant blood-related side effects, such as low white blood cell or platelet counts, imatinib has a history of use. The FDA has already approved it for certain types of leukemia, which supports its overall safety.

Overall, these treatments have been studied and are generally considered safe for many patients, though monitoring for side effects is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Acute Lymphoblastic Leukemia (ALL) because they incorporate novel approaches targeting specific genetic markers. Blinatumomab is an innovative bispecific T-cell engager (BiTE) antibody that connects T-cells to cancer cells, enhancing the body's immune response. Dasatinib and Imatinib are tyrosine kinase inhibitors that target specific proteins involved in cancer cell growth, especially effective in Philadelphia chromosome-positive (Ph+) ALL and other genetic fusion variations. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, these treatments offer a more targeted approach, potentially leading to fewer side effects and better patient outcomes.

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

Research has shown that using blinatumomab and dasatinib together holds promise for treating Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). In one study, 95% of patients remained alive after 18 months, with many showing no signs of the disease. Another study found that over 80% of patients survived long-term, suggesting these drugs could offer lasting benefits. In this trial, participants in Stratum I (Ph+ ALL) will receive blinatumomab and dasatinib.

Additionally, studies have shown that combining blinatumomab and imatinib with chemotherapy can help patients achieve complete remission, meaning no signs of cancer. Participants in Stratum II (PDGFRB ABL-Class fusions) and Stratum III (non-PDGFRB ABL-Class fusions) will receive blinatumomab and imatinib. ^{6 7 8 9 10}

Who Is on the Research Team?

Thai Hoa Tran

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients with a specific type of leukemia called Ph+ or Ph-like ABL-class B-ALL. They must have started treatment but not received more than 14 days of dasatinib, and their cancer cells should express CD19. Patients need to have begun standard chemotherapy and have an acceptable level of physical functioning. Kidney function must also meet certain criteria.

Inclusion Criteria

My test results show I have ABL-class fusions.

I started treatment with specific drugs for my cancer.

I have taken dasatinib for no more than 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive dasatinib and other chemotherapy agents to induce remission

4 weeks

Multiple visits for drug administration

Consolidation

Patients receive dasatinib and blinatumomab to consolidate remission

8 weeks

Multiple visits for drug administration

Interim Maintenance

Patients receive maintenance therapy to prevent relapse

9 weeks

Regular visits for drug administration

Delayed Intensification

Patients receive intensified therapy to eliminate residual disease

9 weeks

Regular visits for drug administration

Maintenance

Long-term maintenance therapy to sustain remission

2 years

Regular visits every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Dasatinib
• Imatinib

Trial Overview The study tests if adding blinatumomab (an antibody that helps the immune system fight cancer) to dasatinib or imatinib (drugs blocking cancer cell growth signals) plus standard chemo works better than just dasatinib/imatinib with chemo in treating this leukemia.

How Is the Trial Designed?

Group I: Stratum III (non-PDGFRB ABL-Class fusions) Experimental Treatment 20 Interventions

See detailed description.

Group II: Stratum II (PDGFRB ABL-Class fusions) Experimental Treatment 20 Interventions

See detailed description.

Group III: Stratum I (Ph+ ALL) Experimental Treatment 18 Interventions

See detailed description

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10927329/

Long-Term Results of the Dasatinib-Blinatumomab Protocol ... At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2016272

Dasatinib–Blinatumomab for Ph-Positive Acute ... At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/838/530283/Immunomodulatory-Effect-of-Dasatinib-Plus

Immunomodulatory Effect of Dasatinib Plus Blinatumomab ... Our study shows that in adult Ph+ ALL front-line treatment with dasatinib and blinatumomab induces a more profound NK, T-NK and Treg immune ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02143414

Study Details | NCT02143414 | Blinatumomab and ... This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124035857

Immunomodulatory Effect of Dasatinib Plus Blinatumomab ... Our study shows that in adult Ph+ ALL front-line treatment with dasatinib and blinatumomab induces a more profound NK, T-NK and Treg immune modulation.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2411680

Blinatumomab in Standard-Risk B-Cell Acute ... Treatment with blinatumomab has been shown to improve outcomes in children with relapsed B-cell acute lymphoblastic leukemia (B-cell ALL).

7. 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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12325004/

Blinatumomab in pediatric B-acute lymphoblastic leukemia Extended follow-up data revealed that patients receiving blinatumomab consolidation therapy maintained event-free survival (EFS) exceeding 50% ...

9. 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 = ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0145212625005880

Efficacy and safety of blinatumomab for CD19 + acute ... One-year OS rates of 66.7 %, 91.7 %, and 22.2 % observed in the frontline, consolidation, and relapsed/refractory settings were similar to rates seen in ...