Inotuzumab Ozogamicin Post-Transplant for Leukemia and Lymphoma

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Leland Metheny, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Leland Metheny

Must not be taking: TKI, Sirolimus

Disqualifiers: Disease progression, Organ dysfunction, GVHD, others

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

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}

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.

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 (Monoclonal Antibodies)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The James Cancer Hospital and Solove Research Institute Columbus, OH

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center Cleveland, OH

Memorial Sloan Kettering Cancer Center New York, NY

University of Nebraska Medical Center Omaha, NE

More Trial Locations

Who Is Running the Clinical Trial?

Leland Metheny Lead Sponsor

References

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

Inotuzumab Ozogamicin in Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. [2020] Despite initial complete remission rates of up to 90%, long-term, disease-free survival remains poor in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Response to salvage chemotherapy is suboptimal; therefore, novel therapeutic agents are being investigated in order to improve outcomes in these patients. Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of adults with relapsed or refractory B-cell precursor ALL. Inotuzumab ozogamicin improves response rate, minimal residual disease negativity, and survival compared to standard chemotherapy in this population. In addition, it offers more opportunities to proceed to an allogeneic stem cell transplant in patients who otherwise may not be candidates.

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

Inotuzumab ozogamicin for the treatment of acute lymphoblastic leukemia. [2019] Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects about 20% of adults with acute leukemia. Historically, those who relapse from this condition have a dismal prognosis. Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. One recent development is the FDA approved therapy inotuzumab ozogamicin which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease. Areas covered: In this review, the pre-clinical and clinical experiences with inotuzumab ozogamicin in lymphoma and ALL are reviewed. The article further includes the published phase I, II and III studies in ALL and considers the safety and efficacy of this treatment. Expert opinion: Inotuzumab ozogamicin is likely to be used, primarily, as a potent agent for relapsed ALL, either as the first choice or for those who fail treatment with blinatumumab. Its potential in newly diagnosed patients is currently unknown, such that the overall impact is likely to be important, but limited.

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

Inotuzumab ozogamicin in the treatment of B-cell acute lymphoblastic leukemia. [2022] Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 monoclonal antibody conjugated with calicheamicin. Preclinical data indicate activity against B-cell tumors and early results from clinical trials indicate activity against B-cell lineage acute lymphoblastic leukemia (ALL).

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] PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.

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

Anti-CD20 and CD22 therapy is effective in non-Hodgkin lymphoma. [2013] Inotuzumab ozogamicin may be more effective than rituximab alone in non-Hodgkin lymphoma.

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] This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m2 on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).

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] The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of inotuzumab ozogamicin (INO) in patients with relapsed/refractory acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL).

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] Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients.

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] The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subsequent haemopoietic stem-cell transplantation (HSCT).

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

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia. [2019] Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin, which is under investigation for the treatment of relapsed/refractory acute lymphoblastic leukemia. CD22 is commonly expressed in 90-100% of malignant mature B-lymphocyte lineage. The first Phase II study with inotuzumab ozogamicin conducted by Kantarjian et al. gave the opportunity for heavily pretreated patients with acute lymphoblastic leukemia to go for allogeneic stem cell transplant. Inotuzumab is well-tolerated with the exception of veno-occlusive disease. Overall inotuzumab ozogamicin is potentially an encouraging and promising therapy for patients.