A Phase 2 Study of Inotuzumab Ozogamicin (CMC-544) in Subjects With IndolentNon-Hodgkin’s Lymphoma (NHL) That is Refractory to or has Relapsed After Rituximab and Chemotherapy or Radioimmunotherapy

• Conditions: Indolent Non-Hodgkin's Lymphoma; MedDRA version: 9.1Level: LLTClassification code 10065856Term: Non-Hodgkin's lymphoma unspecified histology indolent

• Registration Number: EUCTR2008-001635-34-NL
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc., Clinical Research & Development

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-10
• Last Update Posted: 19 August 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Subjects who have been previously diagnosed with CD22-positive, indolent NHL
(defined as follicular, marginal zone, or SLL) that has progressed after =2 prior therapies.
2. Previous anticancer treatment given must have contained rituximab and chemotherapy, or anti CD20 RIT. Subjects must have exhibited no response or have progressed within 6 months from the completion of rituximab or rituximab containing therapy or within 12 months of the completion of RIT.
3. Measurable disease with at least one lymph node or tumor mass >1.0 cm in the greatest transverse diameter (GTD) and the product of the diameters (PD) =2.25cm2 as measured by CT or MRI.
4. Age 18 years or older.
5. Eastern Cooperative Oncology Group (ECOG) performance status =2 (corresponds to Karnofsky Performance Status (KPS) =60%).
6. Life expectancy =12 weeks.
7. Adequate bone marrow function, defined as absolute neutrophil count (ANC) =1.5 x 109/L (=1,500/µL), hemoglobin >9.0 g/L, and platelet count =100 x 109/L (=100,000/µL) with no packed red blood cell (PRBC) or platelet transfusions 2 weeks before the first dose of test article.
8. Serum creatinine =2.0 x upper limit of normal (ULN) and urine protein/creatinine ratio =0.5.
9. Adequate hepatic function, defined as total bilirubin =1.5 x ULN and aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) levels =2.5 x ULN.
10. Negative serum pregnancy test within 1 week before first treatment if the subject is a woman of childbearing potential. 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. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 28 to 42 days after the last dose of test article. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.
12. Signed and dated institutional review board (IRB)/independent ethics committee
(IEC)-approved informed consent form before any screening procedures are performed.
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. Candidate for potentially curative therapies in the opinion of the investigator.
2. History of, or suggestive of, veno-occlusive disease (VOD) or sinusoidal obstruction
syndrome (SOS).
3. Prior allogeneic hematopoietic stem cell transplant (HSCT).
4. Autologous HSCT within the last 6 months before receiving test article.
5. Prior treatment with inotuzumab ozogamicin.
6. Subjects with intolerance to or who have had a severe allergic or anaphylactic reaction to any humanized monoclonal antibodies.
7. Major surgery, not related to debulking surgical procedures, within 28 days before the first dose of test article.
8. Have received any chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational drugs/devices within 28 days before administration of the first dose of test article. Subjects receiving high doses of corticosteroids must have been tapered to a stable dose at least 14 days before the first dose of inotuzumab ozogamicin
9. Pregnant or breastfeeding women.
10. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
11. Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.
12. Current or chronic hepatitis B or hepatitis C infection, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice.
13. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function,
unstable pulmonary condition).
14. Any evidence of serious active infection (eg, requiring an IV antibiotic or antiviral agent within 4 weeks of test article administration; an active infection requiring oral anti-infective agents within 2 weeks of test article administration; or any other history of deep tissue infection suggestive of underlying immune system dysfunction [fascitis, deep tissue abscess, osteomyelitis, articular septic arthritis] within 12 months of test article administration).
15. Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous malignancies are eligible provided that they have been disease free for 2 years or more.
16. Primary effusion lymphoma.
17. Left ventricular ejection fraction (LVEF) that is greater than Grade 1 (NCI CTCAE v3), or the presence of NYHA stage III or IV congestive heart failure.
18. Previous myocardial infarction or pulmonary hypertension within the past 6 months.
19. Known system vasculitides (eg, Wegener granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (eg, severe inflammatory disease).
20. History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
21. Administration of a live vaccine within 6 weeks of the first dose of test article.
22. Any major illness/condition or abnormal laboratory finding that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in the study.

Study & Design

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