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 - ND

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2007-000219-27-IT
• Date of registration: 27/10/2008
• Prospective Registration: No
• Primary sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc
• Public title: 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 - ND
• Scientific title: 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 - ND
• Date of first enrolment: 29/04/2008
• Target sample size: 978
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000219-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, France, Germany, Ireland, Italy, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Subjects with a diagnosis of CD20and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, 2.Prior CD20 and CD22-immunophenotyping of tumors to document B-cell NHL. 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/L) and platelets ≥ 75 x 109/L (75,000/L).
7.Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) and urine protein to creatinine ratio of ≤ 0.2.
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 CT or MRIat the time of inclusion,
10.Negative serum pregnancy test performed within 1 week before administration of the first dose of test article
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.
5.Subjects whose disease is primary rituximab refractory, meaning that they did not have a CR or PR or that they experienced disease progression within 6 months after their first dose of rituximab or rituximab containing treatment regimen.
6.Subjects whose disease is otherwise rituximab refractory, meaning that they did not have a CR or PR or had disease progression within 6 months after their first dose of rituximab within their second course of rituximab or rituximab-containing treatment regimen.
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 at least 1 of the 2 treatment options in arm 2.
11.Cardiac function, as measured by left ventricular ejection fraction (LVEF), is outside of the institutional limits of normal.
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).
15.Known seropositivity for human immunodeficiency virus (HIV); current or chronic hepatitis B or hepatitis C infection.
16. Subjects with a history of veno-occlusive disease or chronic liver disease, such as 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 evidence of serious active infection (ie, requiring an intravenous [IV] antibiotic or antiviral agent).
20. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix.
21. Subjects with previous malignancies are eligible provided that they have been disease free for 5 years or more. Subjects with a history of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ, which have been successfully t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed or refractory follicular B-cell Non Hodgkin`s Lymphoma
MedDRA version: 9.1 Level: LLT Classification code 10029547 Term: Non-Hodgkin's lymphoma
MedDRA version: 9.1 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell

Intervention(s)

Product Name: Inotuzumab Ozogamicin
Product Code: CMC-544
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: inotuzumab ozogamicin
Current Sponsor code: CMC-544
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Mitoxantrone 2mg/ml Sterile Concentrate
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Mitoxantrone
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Trade Name: Fludara 50mg Pwder for Solution for Injection or Infusion
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Fludarabine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: Cyclophosphamide Injection 500 mg
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Vincristine Sulphate 1mg/ml Injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: MABTHERA
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Decortin H 20 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Dexamethason 4mg Galen
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Main Objective: To evaluate efficacy as measured by progression-free survival (PFS), with a goal of demonstrating the superiority of inotuzumab ozogamicin when administered in combination with rituximab, compared with an active comparator arm.

Primary end point(s): The primary efficacy endpoint for this study is PFS assessed by independent radiology and oncology review.Secondary endpoints are to evaluate the efficacy of inotuzumab ozogamicin in combination with rituximab relative to an active comparator arm using the following endpoints and analyses: ORR (complete response [CR] plus unconfirmed complete response [CRu] plus partial response [PR]) and OS. Survival will be recorded from the date of randomization until the time of death, censored at the last date known alive. In addition, the population PK of inotuzumab ozogamicin in combination with rituximab will be evaluated. Finally, health-related quality of life as assessed by FACT-Lym and EQ-5D and subject self-reported fatigue as measured by FACIT-Fatigue will be examined.

Secondary Objective: To evaluate the safety and tolerability of inotuzumab ozogamicin in combination with rituximab
To evaluate the population pharmacokinetics (PK) of inotuzumab ozogamicin in combination with rituximab, and to evaluate factors affecting drug disposition
To evaluate the efficacy of inotuzumab ozogamicin in combination with rituximab using the following endpoints and analyses:
ORR (defined as CR plus unconfirmed complete response [CRu] plus partial response [PR])
Overall survival (OS)

Health-related quality of life as assessed by the Functional Assessment of Cancer Therapy for lymphoma patients (FACT-Lym) and the European Quality of Life-5 Dimensions questionnaire (EQ-5D)
Subject self-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue
QT assessment

Secondary ID(s)

3129K4-3301-WW

2007-000219-27-BE