An Open-Label, Randomized, Phase 3 Study Of Inotuzumab Ozogamicin Administered In Combination With Rituximab Compared To Defined Investigator*s Choice Therapy In Subjects With Relapsed Or Refractory CD22-Positive Aggressive Non-Hodgkin Lymphoma Who Are Not Candidates For Intensive High-Dose Chemotherapy.

Phase 3

Withdrawn

• Conditions: Subject with a diagnosis of CD20 and CD22- positive agressive non-Hodgin lymphoma; cancer of the lymphoid tissue; malign lymphnodes; 10025322

• Registration Number: NL-OMON39239
• Lead Sponsor: Pfizer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Withdrawn
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

1. Subjects with a diagnosis of CD20 and CD22-positive aggressive NHL (based on local immunophenotyping and histopathology) who have:
a. Refractory disease: defined as disease progression while receiving their most recent prior cytotoxic chemotherapy (single-agent immunotherapy as maintenance is not considered cytotoxic therapy);
b. Persistent disease: defined as stable disease or partial response at the completion of their most recent prior cytotoxic chemotherapy;
c. Relapsed/recurrent disease: defined as complete response at the end of their most recent prior cytotoxic chemotherapy with subsequent relapse or disease recurrence.
Eligible aggressive subtypes identified per the 2008 World Health Organization classification include: a) DLBCL (including DLBCL with follicular elements), b) transformed indolent lymphoma with DLBCL, and c) primary mediastinal large B-cell lymphomas.
2. Subjects must have received prior rituximab and may have received up to 3 prior regimens containing cytotoxic chemotherapies for aggressive NHL. In order to ensure consistency in the application of the inclusion criterion:
•Only count regimens that contain 1 or more cytotoxic drug. Do not count palliation with steroids alone, vaccines, non-systemic therapy such as radiation, or maintenance therapies such as rituximab.
•Only count INDUCTION regimens. Do not count maintenance or consolidation therapy.
•If a patient had progression of disease between 2 cytotoxic regimens, they always count as 2 separate regimens.
Note: If a regimen was changed (e.g. because the patient did not tolerate it or for financial reasons) and the patient did not progress before the regimen was changed, it is not counted as a separate regimen.
•If a patient has transformed indolent lymphoma with DLBCL, only count the regimens received for aggressive lymphoma.
3. Subjects must not be candidates for intensive high-dose chemotherapy, with or without an autologous stem cell transplant (aSCT), due to one or more of the following factors: age, comorbid disease, performance status, prior high-dose chemotherapy, or persisting toxicities from prior chemotherapy (*transplant preparatory regimen, eg, BEAM, BEAC).
4. Age 18 years or older (For Japan: Age 20 years or older).
5. Absolute neutrophil count (ANC) >=1.0 x 109/L (1000/µL) and platelets >= 75 x 109/L (75,000/µL), unless related to bone marrow infiltration.
6. Serum creatinine <=1.5 x the upper limit of normal (ULN) (or any serum creatinine level associated with a measured or calculated creatinine clearance of >=40 mL/min).
7. Total bilirubin <=1.5 mg/dL (25.65 µmol/L) unless Gilbert*s syndrome, aspartate and alanine aminotransferase (AST, ALT) <=2.5 x ULN.
8. At least 1 measurable disease lesion that is >=1.0 cm in 2 perpendicular dimensions, with the product diameter >=2.25 cm2 by computed tomography (CT) or magnetic resonance imaging (MRI).
Tumor lesions that are located in a previously irradiated area will be considered measurable only if progression is documented following completion of radiation therapy.

Exclusion Criteria

1. Prior allogeneic hematopoietic stem cell transplant (HSCT).
2. Within <=6 months before first dose of investigational product:
a. Prior treatment with anti-CD22 antibodies;
b. Prior radioimmunotherapy.
3. Prior autologous stem cell transplant within <=4 months before first dose of investigational product.
4. Contraindication to rituximab.
5. Contraindication to both investigator*s choice immuno-chemotherapy regimens.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 4 and/or a life expectancy <12 weeks.
7. Subjects with known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease).
8. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice.
9. History of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
10. Evidence of serious active infection (eg, requiring an intravenous [IV] antibiotic, antiviral, or antifungal agent), or subjects with a recent history of deep tissue infections such as fascitis or osteomyelitis.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Overall survival (OS).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Progression free survival (PFS);<br /><br>- Overall (objective) response rate (ORR);<br /><br>- Duration of response (DoR);<br /><br>- Patient-reported health-related quality of life, lymphoma specific symptoms,<br /><br>and health status for subjects in each treatment arm as measured by the<br /><br>Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) and EuroQol-5D<br /><br>(EQ-5D) questionnaires</p><br>