Inotuzumab Ozogamicin for Leukemia and Lymphoma

Recruiting at 162 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

Trial Summary

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.

What data supports the effectiveness of the drug Inotuzumab Ozogamicin for leukemia and lymphoma?

Inotuzumab Ozogamicin has shown effectiveness in treating B-cell non-Hodgkin's lymphoma and B-cell acute lymphoblastic leukemia, with studies indicating a significant response rate in patients, including those with relapsed or refractory conditions. In one study, the drug achieved an 85% overall response rate in Japanese patients with follicular lymphoma, and it is FDA approved for use in acute lymphoblastic leukemia, suggesting its potential to improve outcomes in these conditions. ^{1 2 3 4 5}

What is the safety profile of Inotuzumab Ozogamicin in humans?

Inotuzumab Ozogamicin has been tested in humans for conditions like non-Hodgkin's lymphoma and acute lymphoblastic leukemia. Common side effects include low platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and nausea. It was generally well tolerated at certain doses, but some patients experienced serious side effects, indicating the need for careful monitoring during treatment. ^{1 2 4 6 7}

What makes the drug Inotuzumab Ozogamicin unique for treating leukemia and lymphoma?

Inotuzumab Ozogamicin is unique because it is an antibody-drug conjugate that specifically targets CD22, a protein found on the surface of B-cell tumors, and delivers a potent toxin called calicheamicin directly to the cancer cells. This targeted approach can improve outcomes for patients with certain types of leukemia and lymphoma compared to standard chemotherapy. ^{1 2 8 9 10}

What is the purpose of this trial?

This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.

Research Team

Maureen M O'Brien

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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, 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 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) 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 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]

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]

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]

References

1. United States 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. [2019]

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

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy. [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 of Inotuzumab Ozogamicin (CMC-544) for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis. [2022]

7. United States 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. [2022]

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

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

9. United States 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. [2021]

10. United States 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. [2023]