Inotuzumab Ozogamicin for Leukemia and Lymphoma

Recruiting at 170 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: Investigational drugs, Anti-GVHD agents

Disqualifiers: Prior SOS, Isolated CNS relapse, 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: 4

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a targeted drug, inotuzumab ozogamicin, for children and young adults with certain blood cancers, specifically B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia, that have returned or are difficult to treat. Inotuzumab ozogamicin is designed to attach to cancer cells and deliver a toxic punch to kill them. The trial includes two groups: one receiving inotuzumab ozogamicin alone, and another receiving it with mBFM chemotherapy. This trial may suit patients under 22 whose cancers have returned or not responded to previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain anti-cancer agents and medications to prevent organ rejection are not allowed, and there are specific waiting periods for some treatments before starting the trial. It's best to discuss your current medications with the study team to understand any necessary changes.

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

Research has shown that inotuzumab ozogamicin is generally safe for people with certain blood cancers, such as leukemia and lymphoma. One study demonstrated its effectiveness for patients whose acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma returned or did not respond to other treatments, with only a few side effects. Another study found that adjusting the dose made it a safe and effective option for adults with B-ALL, a type of leukemia.

When combined with standard chemotherapy, inotuzumab ozogamicin produced promising results. This combination aimed to maintain or improve outcomes for high-risk patients. These studies indicate that while side effects can occur, they are usually manageable for most patients. This suggests that the treatment has undergone sufficient testing to understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard chemotherapy treatments for leukemia and lymphoma, which often involve a broad attack on rapidly dividing cells, inotuzumab ozogamicin targets cancer cells more precisely. This drug is an antibody-drug conjugate, meaning it combines an antibody specifically designed to find and attach to cancer cells with a chemotherapy agent that can directly kill those cells. Researchers are excited about inotuzumab ozogamicin because this targeted approach not only aims to be more effective but also could potentially lead to fewer side effects compared to traditional chemotherapy. Additionally, in one of the treatment arms, the combination with mBFM chemotherapy might enhance its effectiveness by leveraging the strengths of both therapies.

What evidence suggests that inotuzumab ozogamicin might be an effective treatment for leukemia and lymphoma?

Research shows that inotuzumab ozogamicin effectively treats certain blood cancers. Studies found that 74% of patients achieved complete remission, with no signs of cancer, or remission with some recovery still needed. Additionally, 82% of those checked had very low cancer levels after treatment. In this trial, some participants will receive inotuzumab ozogamicin alone, while others will receive it with mBFM chemotherapy. This combination aims to maintain or improve results in patients with high-risk B-cell cancers. These findings suggest that inotuzumab ozogamicin could be a strong option for leukemia and lymphoma that have recurred or are difficult to treat. ^{1 2 3 6 7}

Who Is on the Research Team?

Maureen M O'Brien

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for young patients under 22 with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that's relapsed or resistant to treatment. They must have had prior therapies, be in good physical condition, and not have a history of severe liver issues or certain genetic syndromes. Females of childbearing age must agree to use contraception.

Inclusion Criteria

It has been over 30 days since my last CAR-T cell therapy session.

I had B-cell lymphoma and it has come back, with a current diagnosis of M2 or M3 marrow.

I am between 1 and 21 years old.

Exclusion Criteria

I have had a stem cell transplant before.

I am using effective birth control during and for 8 months after my treatment.

Only individuals who do not have Down syndrome are eligible for Cohort 2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment (Cohort I)

Patients receive inotuzumab ozogamicin intravenously over 60 minutes on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles.

Up to 24 weeks

3 visits per cycle (in-person)

Treatment (Cohort II)

Patients receive inotuzumab ozogamicin and mBFM chemotherapy. Treatment repeats every 42 days for up to 2 cycles.

Up to 12 weeks

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 30 days, every 3 months for 1 year, and then yearly for 4 years.

5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Inotuzumab Ozogamicin

Trial Overview The trial tests Inotuzumab Ozogamicin, an antibody linked to a toxin targeting cancer cells, on younger patients with specific types of leukemia/lymphoma. It aims to see how well it treats those whose disease has returned or hasn't responded after standard treatments.

How Is the Trial Designed?

Group I: Cohort II (inotuzumab ozogamicin, mBFM chemotherapy) Experimental Treatment 13 Interventions

See Detailed Description

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

Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. (COMPLETE)

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?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 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]

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 shows greater effectiveness compared to rituximab alone in treating non-Hodgkin lymphoma, suggesting it may offer a better therapeutic option for patients.

The study indicates that inotuzumab ozogamicin could enhance treatment outcomes, although specific details on the number of subjects or study duration were not provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD20 and CD22 therapy is effective in non-Hodgkin lymphoma. [2013]

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) significantly improved complete remission rates in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL), achieving a 73.8% rate compared to 30.9% with standard-of-care chemotherapy, based on a study of 326 participants.

The median overall survival was also better with InO (7.7 months) compared to standard care (6.2 months), and InO facilitated more patients to proceed to hematopoietic stem cell transplantation, although it was associated with a higher risk of veno-occlusive disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Kantarjian, HM., DeAngelo, DJ., Stelljes, M., et al.[2021]

Inotuzumab ozogamicin, an antibody-drug conjugate targeting CD22, was well tolerated in a phase I study with 13 Japanese patients suffering from relapsed or refractory B-cell non-Hodgkin lymphoma, confirming a maximum tolerated dose of 1.8 mg/m² without dose-limiting toxicities.

The treatment showed promising efficacy, with an overall response rate of 85%, including a 54% complete response rate, indicating its potential as a therapeutic option for patients previously treated with rituximab-containing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy. Ogura, M., Tobinai, K., Hatake, K., et al.[2019]

Inotuzumab ozogamicin (INO) demonstrated significant efficacy in treating relapsed/refractory acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL), with complete remission rates of 67% for ALL and 28% for NHL based on a systematic review of 12 studies involving 644 patients.

The treatment was associated with manageable safety concerns, with notable adverse events including thrombocytopenia and neutropenia, but a relatively low incidence of severe hepatic complications, indicating that INO can be a viable option for patients with these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis. Li, X., Zhou, M., Qi, J., et al.[2022]

In a phase I/II study involving 118 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of inotuzumab ozogamicin and rituximab (R-INO) showed high objective response rates of 87% for relapsed follicular lymphoma and 74% for relapsed diffuse large B-cell lymphoma.

The treatment demonstrated a manageable safety profile, with the most common severe side effects being thrombocytopenia and neutropenia, while achieving a 2-year progression-free survival rate of 68% for follicular lymphoma and 42% for diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. Fayad, L., Offner, F., Smith, MR., et al.[2023]

In a phase I trial involving 19 patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas, the combination of inotuzumab ozogamicin and temsirolimus showed preliminary antitumor activity, with 39% of evaluable patients achieving partial remission.

However, the treatment was associated with significant dose-limiting toxicities, including thrombocytopenia and hypertriglyceridemia, which limited the ability to administer the drugs at therapeutically useful doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas. Pirosa, MC., Zhang, L., Hitz, F., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33461955/

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) ... Conclusions: According to our study, INO was effective in the treatment of relapsed/refractory ALL and NHL with limited adverse effects. High-quality randomized ...

2. 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 ...

3. 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.

4. 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265020310144

Efficacy and Safety of Inotuzumab Ozogamicin (CMC-544) ... Over the past 40 years, outcomes for newly diagnosed patients with ALL and NHL have improved dramatically, with 5-year overall survival rates rising to nearly ...

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

INO-CD22: A multicenter, real-world study of inotuzumab ... Conclusions: Despite the limitations of retrospective studies, the INO-CD22 study highlights the favorable safety profile and clinical activity ...

7. 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.