348 Participants Needed

Blinatumomab + Chemotherapy for Leukemia

Recruiting at 139 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Cancer Institute (NCI)
Must be taking: TKIs, Steroids
No Placebo GroupAll 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 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

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does mention that patients should not have received chemotherapy for B-ALL, except for up to five days of certain medications like hydroxyurea or steroids before starting the trial.

What data supports the effectiveness of the drug Blinatumomab in treating leukemia?

Blinatumomab has been shown to improve survival and complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL) compared to standard chemotherapy. In clinical trials, patients treated with Blinatumomab had a median survival of 7.7 months versus 4.0 months with standard chemotherapy, and a higher complete remission rate of 34% compared to 16% with standard treatment.12345

Is Blinatumomab safe for use in humans?

Blinatumomab has been tested in various clinical trials and is generally considered safe, but it can cause some serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues (problems with the brain and nerves). These side effects are usually manageable with proper medical care.16789

What makes the drug Blinatumomab unique for treating leukemia?

Blinatumomab is unique because it is a bispecific T-cell engager that targets CD19 on leukemia cells and activates T-cells to destroy them, offering a novel approach compared to traditional chemotherapy. It is administered through continuous 28-day infusion cycles, which is different from standard chemotherapy schedules.110111213

Research Team

YO

Yishai Ofran

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

Adults aged 18-75 with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia (ALL) can join this trial. They should be in decent physical shape, not pregnant or breastfeeding, and willing to use contraception. People with active brain involvement by leukemia, unstable epilepsy, other cancers, or those who have already started certain treatments for ALL are excluded.

Inclusion Criteria

AST(SGOT)/ ALT(SGPT) =< 2 X the institutional upper limit of normal (ULN)
My liver enzymes are within twice the normal limit.
Any major side effects from my previous treatments have gone away.
See 30 more

Exclusion Criteria

Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
Patient must not be pregnant or breast-feeding
My epilepsy is stable and does not need treatment.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Induction

Patients receive prednisone and a tyrosine kinase inhibitor (TKI) for 21 days

3 weeks
1 visit (in-person)

Induction Therapy

Patients receive induction therapy with either chemotherapy or blinatumomab, along with steroids and TKI

15 weeks
Multiple visits (in-person)

Re-Induction

Patients who remain MRD positive receive re-induction therapy based on their initial treatment arm

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years
Every 3 months for 2 years, every 6 months for years 3-5, then annually for years 6-10

Treatment Details

Interventions

  • Blinatumomab
  • Cyclophosphamide
  • Cytarabine
  • Dasatinib
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Mesna
  • Methotrexate
  • Ponatinib Hydrochloride
  • Prednisone
  • Vincristine Sulfate
Trial OverviewThe study is testing if adding blinatumomab—a cancer cell growth inhibitor—to the usual treatment of chemotherapy, steroids, and a tyrosine kinase inhibitor is more effective for treating ALL. It's a phase III trial where patients receive either standard care or standard care plus blinatumomab.
Participant Groups
5Treatment groups
Experimental Treatment
Active Control
Group I: Arm E (steroid, TKI, chemotherapy)Experimental Treatment14 Interventions
Patients treated on Arm C who remain MRD positive at the end of induction therapy receive chemotherapy based re-induction which is identical to regimen described for Arm B according to patient's age and the pre-specified chemotherapy arm. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.
Group II: Arm D (steroid, TKI, chemotherapy, immunotherapy)Experimental Treatment12 Interventions
Patients treated on Arm B who remain MRD positive at the end of induction therapy receive blinatumomab based re-induction identical to the regimen described for Arm C. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.
Group III: Arm C (steroid, TKI, chemotherapy, immunotherapy)Experimental Treatment12 Interventions
CYCLE 1: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 29 or 30. CYCLE 2: Patients receive ponatinib PO QD or dasatinib PO QD on days 1-28. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
Group IV: Arm B (steroid, TKI, chemotherapy)Experimental Treatment15 Interventions
See Detailed Description.
Group V: Arm A (steroid, TKI), Single Arm Pre-InductionActive Control9 Interventions
Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21 based on investigator's choice.

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)

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

Blinatumomab has been approved for treating relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL), showing a significant improvement in overall survival and complete remission rates compared to standard chemotherapy, with a median survival of 7.7 months versus 4.0 months for chemotherapy.
In clinical trials, blinatumomab demonstrated a complete remission rate of 34% in Philadelphia chromosome (Ph)-negative ALL and 31% in Ph-positive ALL, while also presenting some adverse events like cytokine release syndrome and neurological issues, although it had fewer cases of neutropenia and infections compared to standard treatments.
FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B-Cell Acute Lymphoblastic Leukemia.Pulte, ED., Vallejo, J., Przepiorka, D., et al.[2019]
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.
Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review).Queudeville, M., Ebinger, M.[2021]
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.
Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date.Hathaway, L., Sen, JM., Keng, M.[2020]

References

FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B-Cell Acute Lymphoblastic Leukemia. [2019]
Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). [2021]
Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date. [2020]
Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. [2018]
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. [2023]
The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]
Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab. [2017]
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. [2020]
Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Delivery of Care for Pediatric Patients Receiving Blinatumomab: A Children's Oncology Group Study. [2023]
Blinatumomab: first global approval. [2020]
12.United Statespubmed.ncbi.nlm.nih.gov
Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. [2021]
Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. [2021]