An Open-Label, Randomized, Phase 3 Study of Inotuzumab Ozogamicin (CMC-544) Administered in Combination With Rituximab Compared to a Defined Investigator’s Choice Therapy in Subjects With Relapsed or Refractory, CD22- Positive, Follicular B-Cell Non Hodgkin’s Lymphoma

Not Applicable

• Conditions: -C82 Follicular lymphoma; Follicular lymphoma; C82

• Registration Number: PER-040-08
• Lead Sponsor: ABORATORIOS WYETH S.A.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-06-09
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

• Subjects with a diagnosis of follicular lymphoma, positive for CD20 / CD22, who received 1 or 2 previous regimens, of which at least 1 included the administration of rituximab (as a single agent or in combination). The diagnoses made within a year of randomization do not need to be repeated. Maintenance therapy with rituximab should be considered part of the previous induction regimen.
• Immunophenotyping of CD20 / CD22 from tumors to document B-cell NHL. If this prior documentation is not available, then the immunophenotype of the current disease must be documented by biopsy or fine-needle aspiration, or by determination of NHL cells positive to CD20 / CD22 in the circulation in the peripheral blood before randomization.
• Age 18 years or older.
• Performance status <2 of the Eastern Cooperative Oncology Group (ECOG).
• Life expectancy> 12 weeks
• Absolute neutrophil count (ANC)> 1.5 x 10 ^ / L (1500 / pL) and platelets> 75 x 10 9 / L (75,000 / uL).
• Serum creatinine <1.5 x upper limit to normal (ULN) and protein to urine creatinine ratio <0.2.
• Total bilirubin <1.5 x ULN, AST and alanine aminotransferase (ALT) <2.5 x ULN. On the days of the dose, subjects should not take any corticosteroid in addition to the previous medication and corticosteroids included in the chemotherapy regimen described in the protocol, as well as no corticosteroid needed for physiological replacement.
• At least 1 measurable disease injury that is> 1.5 cm x 1.5 cm on computed tomography (CT) or magnetic resonance imaging (MRI) at the time of inclusion, in an area without prior radiation therapy or progression documented the disease in an area that was previously irradiated.
• Negative serum pregnancy test performed within 1 week before the administration of the first dose of the test product if the subject is a woman of childbearing age (if the subject is male, this requirement is considered to be fulfilled). A woman of childbearing age is one who has the biological ability to get pregnant. This includes women who use contraceptives or whose partners are sterile or use contraceptives.
• Disposition of subject men and women who are not surgically or postmenopausally sterile to using medically acceptable contraceptive methods during the study, including up to 12 months after the last dose of the test product. Sexually active men and women who take birth control pills should also use a barrier method of contraception.

Exclusion Criteria

• Subjects with allogeneic hematopoietic stem cell transplantation (HSCT).
• Subjects with clinical evidence of transformation in a more aggressive subtype of lymphoma or a follicular lymphoma of stage 3B.
• Subjects with previous antologo transplantation during the 6 months prior to the administration of the first dose of the test product.
• Previous treatment with anti-CD22 antibodies or any previous radioimmunotherapy.
• Subjects whose disease is mainly refractory to rituxiraab, which means that they did not have a CR or PR or that they had progression of the disease within 6 months after the first dose of rituximab O of a treatment regimen with rituximab.
• Subjects whose disease is refractory to rituximab in some other way, meaning that they did not have a CR or PR or had progression of the disease within 6 months after the first dose of rituximab within their second treatment with rituximab or of a regimen of treatment with rituximab.
• Major surgery, not related to debulking surgical procedures, during the 21 days prior to the selection.
• Chemotherapy, immunosuppressive therapy against cancer, radiotherapy, growth factors (except erythiopoietin) or research agents during the 28 days prior to the administration of the first dose of the pmeba product. Subjects receiving high doses of corticosteroids should gradually reduce the doses until they reach a stable and acceptable level at least 28 days before the administration of the first dose of the test product.
• Previous chemotherapy with nitrosureas or mitomycin C in the course of the 6 weeks prior to the administration of the first dose of the test product.
• Subjects who do not meet the requirements to be chosen for at least 1 of the two treatment options in arm 2.
• Cardiac function, as measured by the left ventricular ejection fraction (LVEF), is outside the institutional limits of normal.
• Women who are pregnant or breastfeeding (if the subject is male, this criterion is not considered a requirement).
• NHL of the central nervous system (CNS); A lumbar puncture is not required unless there is a clinical suspicion that the CNS is affected by the NHL.
• People with known systemic vasculitis (eg, Wegener´s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus).
• Known HIV status for human immunodeficiency virus (HIV), current or chronic hepatitis B or hepatitis C infection
• Subjects with a history of veno-occlusive disease or chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or suspected alcohol abuse.
• Subjects with neuropathy> grade 1.
• Uncontrolled or severe unrestrained medical pathology (eg, unstable cardiac function, unstable lung disease, uncontrolled diabetes) or any significant disease or abnormal laboratory result that, at the discretion of the investigator, would increase the risk related to subject participation in the study.
• Any evidence of serious active infection (ie, requiring an antiviral agent or intravenous antibiotic [IV]).
• Concurrent active malignant tumor that is not nonmelanoma skin cancer or carcinoma in situ of the cervix.
• Subjects with previous malignancies can participate in the study as long as they have not had the disease for 5 years or more. Patients with a history of carcinomas, basal or squamous cell carcinomas or carcinoma in situ of the cervix, successfully treated, are not excluded.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br>Outcome name:It is defined as the interval from the date of randomization to the date of disease progression or death from any cause, whichever occurs first, censored on the last date of tumor evaluation.<br>Measure:Progression free Survival (PFS)<br>Timepoints:to the date of disease progression or death from any cause<br>

Secondary Outcome Measures

Name	Time	Method
<br>Outcome name:Defined as Complete Response [CR] plus complete unconfirmed response [CRu] plus partial response [PR])<br>Measure:Overall response rate<br>Timepoints:After the study<br>;<br>Outcome name:Survival will be recorded from the date of randomization until the moment of death, censored on the last date on which it is known that the subject was alive.<br>Measure:Overall Survival (OS)<br>Timepoints:During the study<br>;<br>Outcome name:According to the functional evaluation of cancer treatment for patients with lymphoma (FACT-Lym, see Attachment 1) and the European 5-dimensional questionnaire on quality of life (EQ-5D)<br>Measure:Quality of life related to health<br>Timepoints:During the study<br>