Inotuzumab Ozogamicin Post-Transplant for Leukemia and Lymphoma

Recruiting at 6 trial locations

Overseen By Leland Metheny, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Leland Metheny

Must not be taking: TKI, Sirolimus

Disqualifiers: Disease progression, Organ dysfunction, GVHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 28

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests inotuzumab ozogamicin, an experimental treatment that combines an antibody with chemotherapy, to evaluate its effects after a stem cell transplant in patients with specific types of leukemia and lymphoma. The trial aims to determine safe doses and identify any side effects. Patients who have undergone a stem cell transplant for acute lymphoblastic leukemia (ALL) and meet certain criteria, such as having detectable cancer cells within 45 days post-transplant, may qualify. The trial focuses on those who have relapsed or not responded well to previous treatments. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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 exclude the use of certain drugs like TKI or sirolimus. It's best to discuss your specific medications with the study team.

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

Research has shown that inotuzumab ozogamicin has been tested for safety in patients with acute lymphoblastic leukemia (ALL). Some studies found that patients experienced side effects such as infections and liver problems, including a risk of veno-occlusive disease (VOD). In one study, 48% of patients who received inotuzumab ozogamicin had higher death rates after a transplant compared to 22% in the control group.

Despite these risks, inotuzumab ozogamicin has proven effective against leukemia, particularly when other treatments have failed. While the treatment can be beneficial, considering these possible side effects is important. Prospective trial participants should discuss these risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Inotuzumab ozogamicin is unique because it combines a targeted therapy approach with a cytotoxic agent, specifically designed to attack cancer cells in leukemia and lymphoma. Unlike standard chemotherapy, which affects both healthy and cancerous cells, inotuzumab ozogamicin links a monoclonal antibody to a chemotherapeutic drug, directly targeting and delivering the toxic agent to the CD22-positive cancer cells. This targeted mechanism reduces damage to healthy cells and may result in fewer side effects. Researchers are excited because this precision targeting could improve treatment outcomes and offer a new option for patients who don't respond well to existing therapies.

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

Research has shown that inotuzumab ozogamicin is effective against certain blood cancers, such as leukemia and lymphoma. It has shown promise in treating relapsed or refractory acute lymphoblastic leukemia (ALL), helping when the cancer returns or doesn't respond to previous treatments. In this trial, participants will receive inotuzumab ozogamicin after a transplant. One study found that using inotuzumab ozogamicin post-transplant can be safe and might reduce the chance of the cancer returning. Patients who received this treatment had better response rates, with their cancer shrinking or disappearing more often than in those who didn't receive the drug. Additionally, evidence suggests that some lymphoma patients may experience better long-term outcomes with inotuzumab ozogamicin. ^{3 6 7 8 9}

Who Is on the Research Team?

Leland Metheny, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with CD22-positive Acute Lymphoblastic Leukemia or B-cell Non-Hodgkin's Lymphoma who've had a stem cell transplant. They should be in remission but have minimal residual disease, and must start treatment between T+40 and T+100 days post-transplant. Good organ function and performance status are required.

Inclusion Criteria

My leukemia is CD22-positive.

My leukemia is Philadelphia-like ALL.

I can do most of my daily activities without help.

Exclusion Criteria

I don't have lasting side effects from previous treatments that are moderate or worse.

My organs are not working well enough for the trial.

My condition has worsened before joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation of inotuzumab ozogamicin to determine maximum tolerated dose and recommended Phase 2 dose

Up to 16 weeks

Continuous monitoring for safety and tolerability

Phase II Treatment

Participants receive inotuzumab ozogamicin at the recommended Phase 2 dose for up to 4 cycles

Up to 16 weeks

Repeat cycles every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Inotuzumab Ozogamicin

Trial Overview The study tests the safety of varying doses of Inotuzumab Ozogamicin post-transplant (Phase I) and observes side effects after transplant (Phase II). This drug, which combines an antibody with chemotherapy, targets leukemia and lymphoma cells that have come back or resisted other treatments.

How Is the Trial Designed?

Group I: Inotuzumab Ozogamicin Experimental Treatment 1 Intervention

Phase I: A maximum of 4 cycles will be allowed and doses will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels for participants is 0.1-0.6mg/m\^2. Phase II: Participants will be enrolled until all Phase I participants have been followed and assessed for toxicity for at least 4 weeks after the fourth treatment dose of inotuzumab ozogamicin or 4 weeks after the participant goes off treatment, whichever comes first. Doses to be administered will be determined in the phase I portion of the study. The recommended phase 2 dose is 0.3mg/m2. Repeat cycles every 28 days for up to 4 cycles

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?

Leland Metheny

Lead Sponsor

Trials

6

Recruited

80+

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 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 (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 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, 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 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, 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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11929536/

INO‐CD22: A multicenter, real‐world study of inotuzumab ... With a median follow‐up of 37.2 months, the median overall survival (OS) was 7.9 months (95% CI, 6.08–12.42 months) with a 3‐ and 5‐year OS of ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/6/1384/506928/A-multicenter-study-of-posttransplantation-low

A multicenter study of posttransplantation low-dose ... Posttransplant maintenance with inotuzumab is safe and feasible for patients with ALL who are at high risk of relapse.

3. withpower.com withpower.com/trial/phase-2-precursor-cell-lymphoblastic-leukemia-lymphoma-6-2017-384ed

Inotuzumab Ozogamicin Post-Transplant for Leukemia and ... Inotuzumab Ozogamicin has shown effectiveness in treating B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma, improving response rates and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11001510/

a single center phase 1,2 trial - PMC - PubMed Central Patients with lymphoma who received INO had a trend for a better 5-year OS (93% versus 68%) and PFS (93% versus 58%) than in the control group.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924000132

A multicenter study of posttransplantation low-dose ... Posttransplant maintenance with inotuzumab is safe and feasible for patients with ALL who are at high risk of relapse.

6. 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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06427330

Phase II Study of Post-Transplant Low-Dose Inotuzumab ... To learn about the safety of post-HSCT two dose Inotuzumab Ozogamicin to participants with high risk B cell acute lymphoblastic leukemia(B-ALL).

8. 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, ...

9. aetna.com aetna.com/cpb/medical/data/900_999/0919.html?ref=counterforcehealth.org

Inotuzumab Ozogamicin (Besponsa) - Medical Clinical ... Increased risk of post-transplant non-relapse mortality: In the INO-VATE ALL trial, 48% (79/164) patients in the Besponsa arm and 22% (35/162) patients in the ...