Inotuzumab + Blinatumomab for Acute Lymphoblastic Leukemia

Recruiting at 294 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antidepressants, Antipsychotics

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

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

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: Unknown

64 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 2 3 4 7}

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.

Research Team

Matthew J Wieduwilt

Principal Investigator

Alliance for Clinical Trials in Oncology

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.

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

Treatment Details

Interventions

• Blinatumomab
• Inotuzumab Ozogamicin

Trial Overview 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.

Participant Groups

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)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Inotuzumab ozogamicin (InO) demonstrated significantly higher rates of remission and hematopoietic stem cell transplantation (HSCT) compared to blinatumomab (Blina) in adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL), based on indirect treatment comparisons involving patient-level data from 746 participants.

While both treatments showed similar overall survival rates, the analyses indicated a trend favoring InO for event-free survival, suggesting it may offer better outcomes in terms of remission and subsequent treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect Treatment Comparison of Inotuzumab Ozogamicin Versus Blinatumomab for Relapsed or Refractory Acute Lymphoblastic Leukemia. Proskorovsky, I., Su, Y., Fahrbach, K., et al.[2020]

In a study of 71 patients with relapsed/refractory B-lymphoblastic leukemia, treatment with blinatumomab (Blina) and inotuzumab ozogamicin (InO) resulted in high rates of complete remission (CR), with 63% achieving CR after Blina and 82% after InO, indicating strong efficacy for these immunotherapies.

The median overall survival for patients treated with Blina/InO was 19 months, and the disease-free survival was significantly better for patients with negative minimal residual disease (MRD-) compared to those with positive MRD, highlighting the importance of MRD status in treatment outcomes.

NCBI (Pubmed)

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. Fracchiolla, NS., Sciumè, M., Papayannidis, C., et al.[2023]

In a study of 34 adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), blinatumomab achieved a complete remission (CR) rate of 69%, with 78% of those patients reaching minimal residual disease (MRD) negativity, indicating effective treatment outcomes.

Inotuzumab ozogamicin showed an even higher CR rate of 94% in patients with overt r/r B-ALL, with 67% achieving MRD negativity, suggesting both treatments are highly effective salvage options for this aggressive leukemia.

NCBI (Pubmed)

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. Stelmach, P., Wethmar, K., Groth, C., et al.[2021]

In a study of 29 children with acute lymphoblastic leukaemia (ALL) treated with blinatumomab and/or inotuzumab, the complete remission rate was 47.6%, indicating these therapies can be effective alternatives to traditional chemotherapy, especially in heavily pretreated patients.

Both treatments showed promise in reducing minimal residual disease and delaying further chemotherapy, with manageable safety profiles, as only six patients experienced grade 3 reversible non-haematological toxicity.

NCBI (Pubmed)

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). Fuster, JL., Molinos-Quintana, A., Fuentes, C., et al.[2021]

Blinatumomab showed a median overall survival (OS) of 9.3 months compared to 7.7 months for inotuzumab ozogamicin (InO), suggesting a potential survival benefit for blinatumomab in adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) after adjusting for patient characteristics.

The complete remission (CR) rates were similar between blinatumomab and InO, indicating that while blinatumomab may offer better overall survival, both treatments are comparable in terms of achieving remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Comparison of Blinatumomab vs. Inotuzumab Ozogamicin for Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia. Song, J., Ma, Q., Gao, W., et al.[2021]

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 is estimated to be cost-effective compared to inotuzumab for treating adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, with cost-effectiveness ranging from $4006 to $20,737 per quality-adjusted life-year (QALY) gained.

The analysis was based on a comprehensive model using data from the TOWER and INO-VATE-ALL trials, which included health outcomes like complete remission rates and overall survival, adjusted to match patient populations, indicating a thorough evaluation of both efficacy and economic impact.

NCBI (Pubmed)

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. Delea, TE., Zhang, X., Amdahl, J., et al.[2023]

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]

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]

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]

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]

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]

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]

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]