Blinatumomab + Inotuzumab Ozogamicin + Chemotherapy for Leukemia

Overseen By Elias Jabbour, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, HIV-positive, Ph-positive ALL, 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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating patients with B acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, cytarabine, mercaptopurine, methotrexate, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving blinatumomab, inotuzumab ozogamicin, and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Blinatumomab, Inotuzumab Ozogamicin, and Chemotherapy for treating leukemia?

Research shows that Blinatumomab and Inotuzumab Ozogamicin have improved outcomes in patients with relapsed or refractory acute lymphoblastic leukemia (ALL), with studies indicating they can help achieve remission and serve as a bridge to stem cell transplantation. In children, these drugs have shown promise in reducing disease levels and avoiding further toxic chemotherapy. ^{1 2 3 4 5}

Is the combination of Blinatumomab and Inotuzumab Ozogamicin safe for humans?

Research shows that Blinatumomab and Inotuzumab Ozogamicin have been used safely in treating certain types of leukemia, with some patients experiencing reversible side effects. These treatments have been studied in both adults and children, showing promise as alternatives to traditional chemotherapy. ^{1 2 3 4 6}

What makes the drug combination of Blinatumomab, Cyclophosphamide, and Inotuzumab Ozogamicin unique for treating leukemia?

This drug combination is unique because it combines Blinatumomab, which helps the immune system target cancer cells, with Inotuzumab Ozogamicin, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, and Cyclophosphamide, a traditional chemotherapy drug, offering a multi-faceted approach to treating relapsed or refractory B-cell acute lymphoblastic leukemia. ^{1 2 3 6 7}

Research Team

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with newly diagnosed B acute lymphoblastic leukemia or those who've achieved remission after one chemotherapy course. Eligible participants must have a performance status of 0-3, creatinine ≤2.0 mg/dL, bilirubin ≤2.0 mg/dL, and adequate cardiac function. Exclusions include HIV-positive individuals, active uncontrolled diseases/infections, CNS pathology like epilepsy or stroke, current autoimmune disease with potential CNS involvement, pregnant/nursing women, Philadelphia chromosome-positive ALL.

Inclusion Criteria

I have B-lineage ALL or lymphoblastic lymphoma, untreated or in complete remission after one chemotherapy course.

I can care for myself but may not be able to do heavy physical work.

Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)

Exclusion Criteria

I weigh less than 45 kg.

I do not have active liver or bile duct disease, except for Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease.

I have an autoimmune disease that affects my brain or nervous system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intensive Phase

Patients receive hyper-CVAD regimen including cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine, with optional ofatumumab or rituximab

12 weeks

Multiple visits for IV administration

Blinatumomab and Inotuzumab Ozogamicin Phase

Patients receive blinatumomab and inotuzumab ozogamicin over 4 cycles

24 weeks

Continuous IV administration and bi-weekly visits

Maintenance Phase

Patients may receive maintenance therapy with mercaptopurine, methotrexate, vincristine sulfate, and prednisone, with blinatumomab after every 3 cycles

12 months

Monthly visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Monthly follow-up visits

Treatment Details

Interventions

• Blinatumomab
• Cyclophosphamide
• Inotuzumab Ozogamicin

Trial Overview The study tests blinatumomab and inotuzumab ozogamicin combined with chemotherapy drugs (cyclophosphamide to prednisone) as initial treatment for B acute lymphoblastic leukemia. Blinatumomab modifies the immune system to target cancer cells; inotuzumab ozogamicin delivers toxins directly to cancer cells via CD22 binding.

Participant Groups

Group I: Treatment (blinatumomab, inotuzumab, combination chemotherapy) Experimental Treatment 13 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

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]

In a study of 110 adults with relapsed-refractory acute lymphoblastic leukemia (ALL), the combination of low-intensity mini-Hyper-CVD chemotherapy and inotuzumab resulted in an 83% response rate, with 63% achieving complete response and 82% of responders showing no measurable residual disease.

The addition of sequential blinatumomab improved overall survival rates, with a 3-year overall survival of 52% compared to 34% for those receiving only mini-Hyper-CVD plus inotuzumab, indicating that blinatumomab enhances treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. Kantarjian, H., Haddad, FG., Jain, N., et al.[2023]

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]

Inotuzumab ozogamicin, an antibody-targeted chemotherapy, was found to be effective in treating relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma, with an objective response rate of 39% overall and 68% specifically for follicular NHL.

The maximum-tolerated dose was established at 1.8 mg/m², with thrombocytopenia being the most common side effect, affecting 90% of patients, indicating that while the treatment is effective, careful monitoring of blood cell counts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. Advani, A., Coiffier, B., Czuczman, MS., et al.[2019]

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. England pubmed.ncbi.nlm.nih.gov

Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia. [2023]

6. 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]

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

Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. [2019]