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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of inotuzumab ozogamicin for individuals with B-cell acute lymphoblastic leukemia (ALL) who still have cancer cells after initial treatment. Inotuzumab ozogamicin targets and kills specific cancer cells in the blood. Participants receive the treatment through an IV on designated days, with cycles repeating every few weeks. Individuals with B-cell ALL who have relapsed or not fully cleared cancer cells after initial treatment may be suitable for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from potentially effective therapy.

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.

Is there any evidence suggesting that inotuzumab ozogamicin is likely to be safe for humans?

Research shows that inotuzumab ozogamicin is generally well-tolerated, although some side effects occur. In past studies with adults who have acute lymphoblastic leukemia, common side effects included low platelet counts in 51% of patients and low white blood cell counts in 49% of patients. Monitoring these side effects is important because they can increase the risk of bleeding and infections.

Despite these side effects, the treatment has consistently been safe for different groups of patients, including those starting with different doses and those with varying body weights. While risks exist, many patients find the treatment manageable. Patients should always consult their doctor to understand how these findings might relate to their own health situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Acute Lymphoblastic Leukemia, which often include chemotherapy and corticosteroids, inotuzumab ozogamicin offers a unique approach by using an antibody-drug conjugate. This treatment combines an antibody targeting specific cancer cells with a powerful anti-cancer drug, potentially leading to more precise targeting of the cancer cells while sparing healthy ones. Researchers are particularly excited about its targeted mechanism because it may reduce side effects and improve outcomes for patients who have not responded to traditional therapies.

What evidence suggests that inotuzumab ozogamicin might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that inotuzumab ozogamicin effectively treats B-cell acute lymphoblastic leukemia (ALL) that has returned or not responded to other treatments. In this trial, participants will receive inotuzumab ozogamicin, which demonstrated significant improvement in previous studies, with many achieving complete remission, meaning no signs of cancer were found after treatment. This treatment targets and kills cancer cells with a specific marker called CD22. Patients have tolerated it well, as it does not cause severe side effects. These findings suggest that inotuzumab ozogamicin could be a promising option for patients with B-cell ALL. ^{1 2 3 6 7}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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, 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]

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]

Citations

1. besponsa.pfizerpro.com besponsa.pfizerpro.com/efficacy/adult-clinical-data%E2%80%94ino-vate

BESPONSA® (inotuzumab ozogamicin) CR/CRi | Safety Info Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39882642/

Efficacy and safety of currently approved and lower starting ... The study found that a starting dose of the 1.2 mg/m2/cycle demonstrated efficacy and safety consistent with those of the recommended 1.8 mg/m2/ ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1422/531484/Safety-and-Efficacy-Results-of-Dose-Adjusted

Safety and Efficacy Results of Dose-Adjusted Inotuzumab ... The results of this study indicate that dose-adjusted InO is a well-tolerated and effective treatment option for B-ALL adults with or without chemotherapy or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12533514/

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia Outcomes have been historically poor in adults with relapsed/refractory (R/R) B-cell ALL, with a 5-year overall survival (OS) rate of <10% with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03913559

Inotuzumab Ozogamicin for Children With MRD Positive ... Assess the efficacy of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL with 0.1 - 4.99% blasts in bone marrow. Secondary Objectives. Study the ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6541

Outcomes in patients with B-cell precursor acute ... In this pooled analysis of pts treated with InO for R/R B-ALL, efficacy and safety outcomes were broadly consistent across BMI groups.

7. besponsa.pfizerpro.com besponsa.pfizerpro.com/safety/adult-safety-data

BESPONSA® (inotuzumab ozogamicin) Safety Information In adult patients in the INO-VATE ALL trial, thrombocytopenia and neutropenia were reported in 83/164 patients (51%) and 81/164 patients (49%), respectively.