Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia

Overseen By Elias Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Monoclonal antibodies

Disqualifiers: Pregnancy, HIV, CNS disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

Duration: 18-24 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well inotuzumab ozogamicin works in treating patients with B-cell acute lymphocytic leukemia with positive minimal residual disease. Inotuzumab ozogamicin is a monoclonal antibody called inotuzumab linked to a toxic agent called ozogamicin. Inotuzumab ozogamicin attaches to B cell-specific CD22 cancer cells in a targeted way and kills them.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had monoclonal antibody therapy, radiotherapy, or certain cancer chemotherapies within 2 weeks before starting the study.

What data supports the effectiveness of the drug Inotuzumab Ozogamicin for treating acute lymphoblastic leukemia?

Inotuzumab Ozogamicin has shown better results than standard chemotherapy for patients with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia, improving remission rates and survival chances. It also helps more patients become eligible for stem cell transplants, which can be a crucial step in treatment. ^{1 2 3 4 5}

Is Inotuzumab Ozogamicin safe for humans?

Inotuzumab Ozogamicin has been shown to be generally well-tolerated in patients with acute lymphoblastic leukemia, but some common side effects include blood-related issues and a condition called sinusoidal obstruction syndrome (a liver problem). It has been studied in various trials, and while it shows promise, patients should be aware of these potential risks. ^{1 2 5 6 7}

What makes the drug Inotuzumab Ozogamicin unique for treating acute lymphoblastic leukemia?

Inotuzumab Ozogamicin is unique because it is a targeted therapy that combines an antibody specifically designed to attach to a protein called CD22 on leukemia cells with a powerful toxin, calicheamicin, to kill the cancer cells. This approach is different from standard chemotherapy and has shown better results in patients with relapsed or refractory acute lymphoblastic leukemia, including higher remission rates and improved survival. ^{1 2 4 5 6}

Research Team

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with B-cell acute lymphocytic leukemia showing minimal residual disease after initial treatment. Eligible participants must be in remission but still have detectable cancer cells, have a performance status of 0-2, adequate kidney and liver function, and can include those who've had stem cell transplants. It's not open to pregnant women, HIV+ individuals or those with active infections or other malignancies.

Inclusion Criteria

My ALL is in remission but still shows signs of cancer cells.

I have Philadelphia chromosome-positive ALL and am in my first or second complete remission.

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 X ULN

Exclusion Criteria

Pregnant or nursing women

I haven't had monoclonal antibody therapy in the last 2 weeks.

I haven't had major cancer treatment or experimental drugs in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inotuzumab ozogamicin intravenously over 1 hour on days 1 and 8. Treatment repeats every 21-28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

18-24 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

1 visit at 30 days, then every 6 months

Treatment Details

Interventions

• Inotuzumab Ozogamicin

Trial Overview The study tests Inotuzumab Ozogamicin, an antibody-drug conjugate targeting CD22 on B-cells. This phase II trial aims to see how well it works against leukemia cells that remain after primary therapy. Some patients may also receive tyrosine kinase inhibitors if they have a specific chromosome abnormality.

Participant Groups

Group I: Treatment (inotuzumab ozogamicin) Experimental Treatment 1 Intervention

Patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 8. Treatment repeats every 21-28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Inotuzumab Ozogamicin is already approved in European Union, United States for the following indications:

Approved in European Union as Besponsa for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Approved in United States as Besponsa for:

• Relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older

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 is a promising treatment for adult acute lymphoblastic leukemia (ALL), showing effectiveness as a salvage therapy that can help more patients qualify for stem cell transplants.

Clinical trials indicate that this drug, which targets B-cell tumors, has encouraging response rates, suggesting it could be particularly beneficial for specific subpopulations of ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. Thomas, X.[2022]

Inotuzumab ozogamicin (InO) demonstrated superior clinical activity compared to standard-of-care treatments in patients with relapsed/refractory B-cell acute lymphoblastic leukemia, as shown in the phase 3 INO-VATE trial.

Patients receiving InO reported significantly better quality of life and functioning scores compared to those on standard-of-care, indicating a favorable benefit/risk ratio for InO in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from a phase 3 randomized controlled trial of inotuzumab ozogamicin versus standard therapy for relapsed/refractory acute lymphoblastic leukemia. Kantarjian, HM., Su, Y., Jabbour, EJ., et al.[2019]

Inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate, has been approved for treating adults with relapsed or refractory acute lymphoblastic leukemia (ALL) and shows improved response rates and survival compared to standard chemotherapy.

This treatment not only enhances the chances of achieving minimal residual disease negativity but also increases the likelihood of patients being eligible for allogeneic stem cell transplants, which can be crucial for their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. Williams, S., Kim, M.[2020]

Inotuzumab ozogamicin, a targeted immunotherapy using a CD22 monoclonal antibody, has shown improved complete remission rates and overall survival in adults with relapsed or refractory acute lymphoblastic leukemia (ALL) compared to standard chemotherapy, based on results from Phase 1/2 and Phase 3 clinical trials.

This drug targets CD22, which is present on over 90% of leukemic blasts in ALL patients, highlighting its potential effectiveness and the shift towards using targeted therapies in treating this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Yurkiewicz, IR., Muffly, L., Liedtke, M.[2019]

Inotuzumab ozogamicin, a targeted therapy for relapsed/refractory acute lymphoblastic leukemia, effectively binds to CD22, which is present in 90-100% of malignant B-lymphocytes, showing promise for patients who have undergone extensive prior treatments.

The therapy is generally well-tolerated, although there is a risk of veno-occlusive disease, making it a potentially beneficial option for patients seeking allogeneic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. George, B., Kantarjian, H., Jabbour, E., et al.[2019]

In a subgroup analysis of 55 Asian patients with relapsed or refractory B-cell acute lymphoblastic leukemia, those treated with Inotuzumab ozogamicin (InO) achieved a higher complete remission rate (71%) compared to standard of care (21%).

Patients receiving InO also had a better median overall survival of 5.8 months versus 3.9 months for those on standard treatment, indicating improved efficacy while maintaining a safety profile similar to the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia. Fujishima, N., Uchida, T., Onishi, Y., et al.[2022]

Inotuzumab ozogamicin (InO) is effective and well-tolerated in both younger (<55 years) and older (≥55 years) patients with relapsed/refractory acute lymphoblastic leukemia (ALL), showing similar remission rates and duration of remission across age groups.

Younger patients had a longer overall survival (OS) compared to older patients (8.6 months vs 5.6 months), and older patients experienced a higher incidence of veno-occlusive disease after hematopoietic stem cell transplantation, indicating a need for careful monitoring in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Jabbour, EJ., DeAngelo, DJ., Stelljes, M., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. [2022]

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

Patient-reported outcomes from a phase 3 randomized controlled trial of inotuzumab ozogamicin versus standard therapy for relapsed/refractory acute lymphoblastic leukemia. [2019]

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

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. [2020]

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

Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia. [2022]

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

Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. [2019]