Inotuzumab Ozogamicin for Acute Lymphoblastic Leukemia

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Torsades de Pointes

Disqualifiers: CNS leukemia, Hepatitis B/C, HIV, 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: Unknown

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether adding the drug inotuzumab ozogamicin to the usual treatment can help patients with a specific type of leukemia (Ph+ ALL) achieve remission faster. The study focuses on patients who are beginning their treatment. Inotuzumab ozogamicin is a medication approved for certain types of leukemia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow limited prior treatment with corticosteroids or hydroxyurea. Medications known to cause heart rhythm issues (Torsades de Pointes) are not allowed during the study.

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

Inotuzumab Ozogamicin has shown to improve response rates, survival, and the ability to proceed to stem cell transplants in patients with relapsed or refractory acute lymphoblastic leukemia compared to standard chemotherapy. It is a promising therapy that targets specific cancer cells, leading to better outcomes for patients who have not responded to other treatments. ^{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 it can cause some side effects, including liver-related issues like veno-occlusive disease (a condition where small veins in the liver are blocked) and sinusoidal obstruction syndrome (a blockage of small veins in the liver). ^{1 2 6 7 8}

How is the drug Inotuzumab Ozogamicin different from other treatments for acute lymphoblastic leukemia?

Inotuzumab Ozogamicin is unique because it is a targeted therapy that uses a monoclonal antibody to deliver a toxic agent directly to cancer cells expressing CD22, which is present in over 90% of acute lymphoblastic leukemia cases. This approach allows for more precise targeting of cancer cells compared to traditional chemotherapy, potentially improving outcomes for patients with relapsed or refractory disease. ^{2 4 9 10 11}

Research Team

Wendy Stock, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults with newly diagnosed Philadelphia chromosome-positive (Ph+) B-cell Acute Lymphoblastic Leukemia. Participants must have CD22 expression on their cancer cells, be in good physical condition as measured by ECOG status, and have proper organ function. Pregnant or breastfeeding individuals are excluded, as well as those with severe medical conditions, certain heart issues, liver disease, active infections or other cancers.

Inclusion Criteria

A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active

My leukemia involves more than 20% lymphoblasts in my bone marrow or blood, confirmed by specific genetic tests.

My organs are functioning well according to my medical records.

Exclusion Criteria

My leukemia has spread to my brain or spinal cord.

History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse

I am not taking any medications that can cause heart rhythm problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Phase

Participants receive inotuzumab ozogamicin combined with anti-cancer drugs for induction therapy

4 weeks

Weekly visits for drug administration

Consolidation Phase

Continuation of treatment with inotuzumab ozogamicin and anti-cancer drugs based on response to induction

4 weeks

Weekly visits for drug administration

Interim/Maintenance Phase

Participants receive maintenance treatment with dasatinib and other drugs, with inotuzumab ozogamicin added in the fourth course

12-24 weeks

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Inotuzumab ozogamicin

Trial Overview The study tests whether adding Inotuzumab Ozogamicin (InO) to standard induction therapy leads to quicker complete molecular remission in Ph+ ALL patients who haven't been treated before. It aims to improve the effectiveness of initial treatment by using this additional anti-cancer drug.

Participant Groups

Group I: Treatment Arm - Interim/Maintenance Phase - Participants in CMR Experimental Treatment 7 Interventions

This study arm is for participants who no longer show any detectable signs of BCR-ABL1 (a cancer-causing gene) in response to the previous phase of induction/consolidation treatment (also known as being in "complete molecular remission" or CMR). Participants in this arm will receive 3 courses of interim/maintenance treatment using dasatinib combined with other anti-cancer drugs. Inotuzumab ozogamicin will be added during the fourth course of treatment. These treatments will be given in 28-day and 84-day cycles. If the participant achieves complete molecular remission (no signs of BCR-ABL gene) after 60 days (or more) of treatment, then the treating physician may take the participant off the study for allogenic stem cell transplantation surgery. If the participant does not undergo allogeneic stem cell transplantation after achieving complete molecular remission, they will complete 3 additional courses of maintenance treatment.

Group II: Treatment Arm - Interim/Maintenance Phase - Participants Not in CMR Experimental Treatment 7 Interventions

This study arm is for participants whose cancer responded to induction/consolidation treatment, but still shows detectable signs of BCR-ABL1 (a cancer-causing gene), so they are not in complete molecular remission. Participants in this arm will receive 3 courses of treatment using ponatinib combined with other anti-cancer drugs. Inotuzumab ozogamicin will be added during the 4th treatment course. These treatments will be given in 28-day and 84-day cycles. If the participant achieves complete molecular remission (no signs of BCR-ABL gene) after 60 days (or more) of treatment, the treating physician may take the participant off the study for allogenic stem cell transplantation surgery. If the participant does not undergo allogeneic stem cell transplantation after achieving complete molecular remission (CMR), they will complete 3 additional courses of maintenance treatment. If the participant doesn't achieve CMR after 4th treatment course, they will be removed from the study.

Group III: Treatment Arm - Induction/Consolidation Phase - All Participants Experimental Treatment 4 Interventions

All participants in this arm will receive the same first round of treatment as part of induction/consolidation therapy. This treatment will use inotuzumab ozogamicin combined with anti-cancer drugs. The additional treatment that participants receive after this first round of treatment will vary based on the participant's response to induction therapy. This phase of treatment will last for 60 days. All participants in this arm will receive the following treatment: Treatment Course I (Induction Phase, 28 days): * Dasatinib 140mg daily continuous * Dexamethasone 10mg/m\^2 PO or IV Days 1-7 and Day 15-Day 22 * InO 0.8mg/m2 Day 8; 0.5mg/m2 D15, 0.5mg/m2 Day 22 * Intrathecal methotrexate 15mg Day 1, Day 28 Treatment Course II (Consolidation Phase, 28 days): * Dasatinib 140mg daily continuous * InO: If in CR/CRi 0.5mg/m2 Day 1, Day 8, Day 15; If not in CR/CRi 0.8mg/m2 on Day 1, 0.5mg/m2 Day 8 and Day 15 * Intrathecal methotrexate 15mg Day 1, Day 28

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

Approved in United States as Besponsa for:

• Adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• Pediatric patients 1 year and older with relapsed or refractory CD22-positive BCP-ALL

Approved in European Union as Besponsa for:

• Adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL)

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

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 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 (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 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 is an FDA-approved therapy that shows promise in treating relapsed acute lymphoblastic leukemia (ALL), potentially reducing toxicity compared to traditional intensive treatments and increasing the chances of achieving minimal residual disease.

The review highlights that inotuzumab ozogamicin may become a primary treatment option for relapsed ALL patients, especially those who do not respond to blinatumumab, although its effectiveness in newly diagnosed cases remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. Tvito, A., Rowe, JM.[2019]

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]

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 treatment resulted in a higher frequency of hepatotoxicity (51%) compared to standard care (34%) in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, indicating a significant safety concern.

The incidence of severe sinusoidal obstruction syndrome was notably higher in the inotuzumab ozogamicin group (13%) compared to the standard care group (<1%), particularly after subsequent hematopoietic stem-cell transplantation, highlighting the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Kantarjian, HM., DeAngelo, DJ., Advani, AS., et al.[2022]

Inotuzumab ozogamicin is an effective treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL), as demonstrated in the phase III INO-VATE trial, which led to its approval for this high-risk group.

This antibody-drug conjugate works by targeting CD22 on tumor cells, leading to cell death, and ongoing trials are exploring its use in combination with low-dose chemotherapy and in earlier treatment stages to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia. Choudhry, A., O'Brien, SM.[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, an anti-CD22 antibody-drug conjugate, has shown improved outcomes in adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) compared to standard salvage chemotherapy.

The combination of inotuzumab ozogamicin with low-intensity chemotherapy is showing promise for both relapse settings and as a frontline treatment for elderly patients, potentially reducing toxicity while enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. Savoy, JM., Welch, MA., Nasnas, PE., et al.[2021]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. [2019]

6. 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]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. [2022]

9. Spain pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of patients with acute lymphocytic leukemia. [2019]

10. England pubmed.ncbi.nlm.nih.gov

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

11. England pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. [2021]