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

• Conditions: Relapsed or refractory, CD22-Positive, follicular B-cell Non Hodgkin's Lymphoma; MedDRA version: 9.1Level: LLTClassification code 10029473Term: Nodular (follicular) lymphoma

• Registration Number: EUCTR2007-000219-27-PT
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-03-27
• Last Update Posted: 26 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 978

Inclusion Criteria

1. Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination). Diagnoses made within 1 year of randomization do not need to be repeated. Maintenance therapy with rituximab should be considered part of the preceding induction regimen (where rituximab maintenance is available, it is the expectation that patients enrolled in this study will have either relapsed during/after a rituximab maintenance containing regimen or would not be considered to benefit from rituximab maintenance).

2. Prior CD20 and CD22-immunophenotyping of tumors to document B-cell NHL. If such prior documentation is not available, then the immunophenotype of the current disease must be documented by fine-needle aspirate or biopsy, or by circulating CD20 and CD22-positive NHL cells from peripheral blood before randomization.

3. Age 18 years or older.

4. Eastern Cooperative Oncology Group (ECOG) performance status = 2.

5. Life expectancy = 12 weeks.

6. Absolute neutrophil count (ANC) = 1.5 x 109/L (1500/microL) and platelets = 75 x 109/L (75,000/microL).

7. Serum creatinine = 1.5 x the upper limit of normal (ULN) and urine protein to creatinine ratio of = 0.5.

8. Total bilirubin =1.5 x ULN, AST and alanine aminotransferase (ALT) = 2.5 x ULN.

9. At least 1 measurable disease lesion that is = 1.5 cm x 1.5 cm by computed tomography (CT) or magnetic resonance imaging (MRI) at the time of inclusion, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.

10. Negative serum pregnancy test performed within 1 week before administration of the first dose of test article if the subject is a woman of childbearing potential (if the subject is male, this criterion is considered to be met). A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.

11. Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study, including up to 12 months after the last dose of test article. Sexually active males and females using oral contraceptive pills should also use barrier contraception.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects with a prior allogeneic hematopoietic stem cell transplant (HSCT).

2. Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B follicular lymphoma.

3. Subjects with prior autologous transplant within 6 months before administration of the first dose of test article.

4. Prior treatment with anti-CD22 antibodies or any previous radio-immuno therapy within 6 months before the administration of the first dose of test article.

5. Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.

6. Subjects with intolerance to rituximab or who have had a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies.

7. Major surgery, not related to debulking surgical procedures, within 21 days before screening.

8. Chemotherapy, cancer immunosuppressive therapy, radiotherapy, growth factors (except erythropoietin), or investigational agents within 28 days before administration of the first dose of test article. Subjects receiving high doses of corticosteroids must have had their doses tapered to a stable and acceptable level at least 28 days before administration of the first dose of test article. On dose days, subjects should not take any corticosteroids apart from the premedication and corticosteroids included in the prescribed chemotherapy regimen described by the protocol, as well as any corticosteroids needed for physiological replacement.

9. Prior chemotherapy with nitrosoureas or mitomycin C within 6 weeks before administration of the first dose of test article.

10. Subjects who are not eligible for either of the 2 treatment options in arm 2.

11. Cardiac function, as measured by left ventricular ejection fraction (LVEF), of less than 50% or the presence of NYHA stage III or IV congestive heart failure, or a previous myocardial infarction within 6 months of test article administration.

12. Female subjects who are pregnant or breastfeeding (if the subject is male, this criterion is considered to be not met).

13. Central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.

14. 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).

15. Current or chronic hepatitis B or hepatitis C infection; known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice.

16. Subjects with a history of veno-occlusive disease or chronic liver disease, as evidenced by otherwise unexplained hypoalbuminemia, elevated prothrombin time or elevated liver function tests. Subjects with cirrhosis or chronic hepatitis due to any cause, or are suspected of alcohol abuse.

17. Subjects with > grade 1 neuropathy.

18. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk associated with the subject’s participation in the study.

19. Any

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified