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

Trial Summary

What is the purpose of this trial?

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects. The Phase II portion of this study is to see what side effects are seen with medication after transplant. Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin is considered experimental in this study.

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.

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

Inotuzumab Ozogamicin has shown effectiveness in treating B-cell acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma, improving response rates and survival compared to standard chemotherapy. It is particularly beneficial for patients with relapsed or refractory B-cell precursor ALL, offering more opportunities for stem cell transplants. ^{1 2 3 4 5}

Is Inotuzumab Ozogamicin safe for humans?

Inotuzumab Ozogamicin has been studied for safety in patients with certain types of leukemia and lymphoma. Common side effects include low platelet counts (thrombocytopenia), weakness (asthenia), and nausea. Some patients also experienced liver-related side effects, especially after a stem-cell transplant. ^{4 6 7 8 9}

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

Inotuzumab Ozogamicin is unique because it is an antibody-targeted chemotherapy that specifically targets the CD22 protein on B-cells, delivering a potent toxin directly to cancer cells, which may reduce overall toxicity compared to traditional chemotherapy. This targeted approach is particularly promising for patients with relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma. ^{2 3 4 7 10}

Research Team

Leland Metheny, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

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.

Patients with evidence of donor chimerism after allogeneic transplantation

Exclusion Criteria

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

My condition has worsened before joining this study.

My organs are not working well enough for the trial.

Timeline

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

Treatment Details

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.

Participant Groups

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+

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 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 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 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]

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 (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]

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, 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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

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

6. 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]

7. 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]

8. 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]

9. 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]

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

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