Blinatumomab + Chemotherapy for Leukemia

Recruiting at 164 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: TKIs, Steroids

Disqualifiers: Pregnancy, Active infection, Unstable epilepsy, 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: 4

348 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether adding blinatumomab to the standard leukemia treatment of chemotherapy, steroids, and TKIs more effectively stops cancer cells than the standard treatment alone. Blinatumomab, a type of immunotherapy, targets cancer cells to prevent their growth and spread. The trial includes different groups for treatment comparison, with some receiving only the standard drugs and others also receiving blinatumomab. Individuals newly diagnosed with B-ALL and a positive BCR-ABL1 marker may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Previous studies have generally considered blinatumomab safe. It primarily treats certain types of leukemia but can cause serious side effects like infections and low white blood cell counts. Doctors are aware of these side effects and manage them during treatment.

Ponatinib, another treatment in this trial, has become safer over time but still carries risks such as heart problems and bleeding. Healthcare providers carefully monitor these issues.

Dasatinib can also cause serious side effects, including liver problems and an increased risk of high blood pressure in the lungs. Doctors monitor these risks closely.

These treatments are closely monitored in clinical trials. Doctors take extra steps to manage side effects and ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about blinatumomab combined with chemotherapy for leukemia because it offers a fresh approach to treating this condition. Unlike traditional therapies, blinatumomab is a bispecific T-cell engager (BiTE) that helps the immune system target and destroy leukemia cells more effectively. This immunotherapy works by connecting T-cells, the body's natural defenders, directly to cancer cells, allowing for a more precise attack. Additionally, this combination treatment includes targeted therapies like Ponatinib and Dasatinib, which are known for their ability to specifically shut down pathways that leukemia cells use to grow. This multi-pronged strategy offers a promising alternative to standard chemotherapy, potentially leading to better outcomes for patients.

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

Research has shown that adding blinatumomab to chemotherapy can greatly improve outcomes for leukemia patients. In this trial, some participants will receive blinatumomab as part of their treatment regimen. One study found that all patients achieved complete or nearly complete remission, with 87.2% having no detectable cancer cells after two treatment cycles. Blinatumomab has also been associated with a 96% chance of being disease-free for three years in some patients. Another treatment option in this trial, ponatinib, demonstrated a 98% survival rate over three years, compared to 58% with a different treatment. For dasatinib, another treatment option in this trial, a study reported an 82% survival rate at four years. These findings suggest that using these treatments together in the various arms of this trial may significantly improve survival and remission rates for leukemia. ^{6 7 8 9 10}

Who Is on the Research Team?

Yishai Ofran

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Cyclophosphamide
• Cytarabine
• Dasatinib
• Dexamethasone
• Doxorubicin Hydrochloride
• Mesna
• Methotrexate
• Ponatinib Hydrochloride
• Prednisone
• Vincristine Sulfate

Trial Overview

The 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.

How Is the Trial Designed?

Group I: Arm E (steroid, TKI, chemotherapy) Experimental Treatment 14 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 Treatment 12 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 Treatment 12 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 Treatment 15 Interventions

See Detailed Description.

Group V: Arm A (steroid, TKI), Single Arm Pre-Induction Active Control 9 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)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A survey of 150 Children's Oncology Group institutions revealed that most patients receiving blinatumomab for B-lineage acute lymphoblastic leukemia are treated in outpatient settings, with only 9% requiring hospitalization for the full 28-day infusion cycle.

There is significant variability in hospitalization practices, with smaller institutions tending to report longer stays, highlighting the need for standardization in care coordination for blinatumomab administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of Care for Pediatric Patients Receiving Blinatumomab: A Children's Oncology Group Study. Withycombe, JS., Kubaney, HR., Okada, M., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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 (BLINCYTO™) is a bispecific T-cell engaging antibody that effectively targets CD19 on B-cell cancers, activating T cells to induce cell lysis, making it a promising treatment for hematological cancers.

Approved by the US FDA in December 2014 for relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), blinatumomab is currently undergoing further development and awaiting EU approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: first global approval. Sanford, M.[2020]

Blinatumomab pharmacokinetics were effectively modeled using a one-compartment linear model, showing a clearance rate of 2.22 L/h and a central volume of 5.98 L, based on data from 674 patients.

Body surface area (BSA) significantly affects the clearance of blinatumomab, particularly in pediatric patients, suggesting that BSA-based dosing is important for lighter patients to ensure effective treatment while minimizing variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clements, JD., Zhu, M., Kuchimanchi, M., et al.[2021]

Blinatumomab is an effective treatment for relapsed or refractory B-acute lymphoblastic leukemia (ALL), particularly in patients with minimal residual disease, as it engages T-cells to target CD19 positive B cells.

While it shows promise, blinatumomab can cause significant adverse effects, including infections and neurotoxicity, requiring careful management by experienced medical centers during its continuous four-week infusion administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab. Wilke, AC., Gökbuget, N.[2017]

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]

Blinatumomab shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

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]

In a phase 2 study, blinatumomab demonstrated a significant overall survival benefit for patients with relapsed/refractory Ph(-) B-precursor acute lymphoblastic leukemia, with a mean survival of 76.1 months compared to 39.8 months for historical patients receiving standard chemotherapy.

At 60 months, 12.6% of patients treated with blinatumomab were still alive, which is more than double the 5.4% survival rate of historical controls, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.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. Barlev, A., Lin, VW., Katz, A., et al.[2021]

In the phase 3 TOWER study, blinatumomab showed a significant overall survival benefit compared to standard-of-care chemotherapy in adults with relapsed or refractory Philadelphia chromosome-negative B-precursor acute lymphoblastic leukemia, involving 267 patients who received a median of 2 cycles of treatment.

After adjusting for treatment duration, blinatumomab had lower exposure-adjusted event rates for serious adverse events compared to standard chemotherapy, particularly for infections and cytopenias, indicating it is a well-tolerated treatment option despite a higher rate of cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. Stein, AS., Larson, RA., Schuh, AC., et al.[2020]

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]

Blinatumomab, a bispecific T-cell engager, has shown a 43% response rate in adult patients with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia, with 40% of responders achieving complete remission and proceeding to stem cell transplantation.

Management strategies, such as premedication with dexamethasone and gradual dose escalation, have successfully reduced the incidence and severity of adverse effects like cytokine release syndrome and neurotoxicity associated with early use of blinatumomab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. Folan, SA., Rexwinkle, A., Autry, J., et al.[2018]

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]

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Blincyto Effective as Initial Treatment for Childhood ALL - NCI

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Safety and Efficacy of Blinatumomab- Real World Data | Blood

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Safety and Efficacy of Blinatumomab- Real World Data

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Adults with Acute Lymphoblastic Leukemia

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