Inotuzumab + Blinatumomab for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

+112 other locations

Overseen by Matthew J Wieduwilt

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: CNS leukemia, Cardiac disease, Liver disease, Neurologic disorder, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back, or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain prior treatments for leukemia must be completed at least 14 days before starting the trial, with some exceptions like intrathecal chemotherapy and corticosteroids, which must be completed 24 hours before starting the trial.

What data supports the effectiveness of the drug combination Inotuzumab and Blinatumomab for treating Acute Lymphoblastic Leukemia?

Research shows that using Blinatumomab and Inotuzumab Ozogamicin together has improved outcomes for patients with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia. In children, these drugs helped achieve complete remission in nearly half of the cases and were useful in reducing disease levels before stem cell transplantation.

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Is the combination of Inotuzumab and Blinatumomab safe for humans?

Blinatumomab has been associated with serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues (such as seizures) in children with leukemia. Inotuzumab has been used in children with leukemia, and some experienced reversible non-blood-related toxicities. Both drugs have been used in heavily pretreated patients, showing some safety concerns but also potential benefits.

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How is the drug combination of Inotuzumab and Blinatumomab unique for treating acute lymphoblastic leukemia?

The combination of Inotuzumab and Blinatumomab is unique because it uses two different targeted therapies to treat relapsed or refractory acute lymphoblastic leukemia (ALL), offering an alternative to traditional chemotherapy. These drugs work by targeting specific proteins on cancer cells, potentially reducing the need for more toxic treatments and improving outcomes for patients who have not responded to other therapies.

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Eligibility Criteria

This trial is for patients with CD22-positive B-lineage acute lymphoblastic leukemia (ALL) that's new, returned, or resistant to treatment. Eligible participants must not have active central nervous system (CNS) leukemia and should be negative for the Philadelphia chromosome/BCR-ABL1. They need a bone marrow sample sent to HEME Biobank before joining.

Inclusion Criteria

The cerebrospinal fluid (CSF) shows abnormal levels of white blood cells (WBC) or red blood cells (RBC) with abnormal findings in a special test called cytospin for cancer cells.

I received a specific spinal injection before joining the trial and started chemotherapy within 7 days after that.

I have been diagnosed with precursor B-cell acute lymphoblastic leukemia, not Burkitt lymphoma.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Patients receive inotuzumab ozogamicin intravenously over 1 hour on days 1, 8, and 15. Treatment continues for 1 course (28 days) in the absence of disease progression or unacceptable toxicity.

4 weeks

Consolidation Treatment

Patients receive blinatumomab IV continuously on days 1-28 and 43-70. Treatment continues for 1 course (84 days) in the absence of disease progression or unacceptable toxicity.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Participant Groups

The study tests how well two monoclonal antibodies, inotuzumab ozogamicin and blinatumomab, treat ALL by helping the immune system attack cancer cells and preventing their growth. It's a phase II trial focusing on those who haven't responded well to previous treatments or are newly diagnosed.

Group I: Cohort 2 (inotuzumab ozogamicin, blinatumomab) Experimental Treatment 2 Interventions

See Detailed Description.

Group II: Cohort 1 (inotuzumab ozogamicin, blinatumomab) Experimental Treatment 2 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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Thomas Jefferson University Hospital Philadelphia, PA

University of Wisconsin Hospital and Clinics Madison, WI

University of Alabama at Birmingham Cancer Center Birmingham, AL

Saint Joseph Mercy Canton Canton, MI

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia. [2020] No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies.

2. Switzerland pubmed.ncbi.nlm.nih.gov

Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study. [2023] Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy.

3. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis. [2021] Blinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

4. England pubmed.ncbi.nlm.nih.gov

Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP). [2021] Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non-haematological toxicity. The 12-month overall survival and event-free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab.

5. United States pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison of Blinatumomab vs. Inotuzumab Ozogamicin for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia. [2021] In the absence of head-to-head trials, this analysis aimed to provide a fair indirect comparison of the efficacy between blinatumomab and inotuzumab ozogamicin (InO), two treatments for adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) who received no more than one prior salvage therapy, by adjusting for cross-trial differences.

6. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022] Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.

7. New Zealand pubmed.ncbi.nlm.nih.gov

Cost Effectiveness of Blinatumomab Versus Inotuzumab Ozogamicin in Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia in the United States. [2023] The TOWER and INO-VATE-ALL trials demonstrated the efficacy and safety of blinatumomab and inotuzumab ozogamicin (inotuzumab), respectively, versus standard-of-care (SOC) chemotherapy in adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). The cost effectiveness of blinatumomab versus inotuzumab has not previously been examined.