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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new anti-cancer drug, inotuzumab ozogamicin, to determine its effectiveness in treating Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The researchers aim to discover if adding this drug to the usual treatment helps patients reach remission faster, making their disease undetectable. Participants must be newly diagnosed with Ph+ ALL and have not received any prior treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inotuzumab ozogamicin (InO) has produced mixed safety results in past studies. Some patients have tolerated it well, but risks remain. One serious potential side effect is veno-occlusive disease (VOD), which affects the liver. Infection is another common concern. In adults with certain types of leukemia, reported side effects include fever and low blood counts. Despite these risks, previous patients found the treatment effective when doses were adjusted. Considering these factors and discussing them with a healthcare provider is important when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute lymphoblastic leukemia?

Unlike standard treatments for acute lymphoblastic leukemia (ALL), which often include chemotherapy and tyrosine kinase inhibitors, inotuzumab ozogamicin offers a unique approach by targeting a specific protein on cancer cells called CD22. This allows for a more direct attack on the cancer cells, potentially leading to better outcomes. Researchers are excited about this treatment because it combines inotuzumab ozogamicin with other anti-cancer drugs to enhance effectiveness, particularly in patients who have not achieved complete molecular remission. This targeted approach, along with its ability to be integrated into various phases of treatment, sets it apart from more traditional therapies.

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

Studies have shown that inotuzumab ozogamicin (InO) effectively treats certain types of leukemia. In earlier research, about 74% of patients achieved complete remission, meaning their cancer was no longer detectable, or remission with some remaining symptoms. Additionally, around 82% of patients had very low levels of cancer cells left, known as minimal residual disease (MRD). These results suggest that InO effectively reduces cancer cells and helps patients reach remission. In this trial, all participants will receive InO as part of their treatment regimen, which may benefit those newly diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). ^{3 4 6 7 8}

Who Is on the Research Team?

Wendy Stock, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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) 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]

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 (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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427359/

Real‐World Data on Inotuzumab Ozogamicin for Adult ... Complete remission or remission with incomplete recovery (CR/CRi) was achieved in 74% of patients. Among those evaluated, 82% reached MRD < 0.01 ...

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

BESPONSA® (inotuzumab ozogamicin) CR/CRi | Safety Info In the remission analysis population of 109 patients randomized to receive BESPONSA, 73% (n=64/88) responded in Cycle 1 and 24% (n=21/88) responded in Cycle 2.

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 ... Conclusions: The results of this study indicate that dose-adjusted InO is a well-tolerated and effective treatment option for B-ALL adults with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40120068/

INO-CD22: A multicenter, real-world study of inotuzumab ... The INO-CD22 study is a multicenter retrospective cohort study of adult patients with relapsed/refractory B-ALL treated with IO in 24 Italian centers from 2014 ...

5. haematologica.org haematologica.org/article/view/11921

Efficacy and safety of currently approved and lower starting ... The prognosis for adults with relapsed/refractory (R/R) ALL is poor, with 20-40% overall survival at 5 years., Currently, the main curative ...

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

BESPONSA® (inotuzumab ozogamicin) Safety Information Adult Safety Data · BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM · The most common (≥2%) serious adverse reactions (ARs) were infection, febrile ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12165494/

Safety evaluation of inotuzumab ozogamicin This study underscores the potential ADEs and associated risks with the clinical application of InO, with particular emphasis on the risks of VOD, infections, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03913559

Inotuzumab Ozogamicin for Children With MRD Positive ... Study the safety of inotuzumab ozogamicin when used in patients with MRD - positive CD22+ B-ALL with < 5 % blasts in bone marrow. Estimate the incidence, ...