A study in patients with Non-Hodgkin Lymphoma (NHL) to evaluate safety and effectiveness of a new drug combination compared to 2 other drug combinations that have already been studied in clinical trials. This study will include patients who have already received therapy for their NHL (but it returned or was not completely cured), and now intense chemotherapy is not the best treatment option due to reasons like health or age. The types of NHL include Diffuse Large B-Cell Lymphoma and others.

• Register: EUCTR
• Last refreshed on: 30 June 2014
• Main ID: EUCTR2010-020147-12-GB
• Date of registration: 04/02/2011
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017
• Public title: A study in patients with Non-Hodgkin Lymphoma (NHL) to evaluate safety and effectiveness of a new drug combination compared to 2 other drug combinations that have already been studied in clinical trials. This study will include patients who have already received therapy for their NHL (but it returned or was not completely cured), and now intense chemotherapy is not the best treatment option due to reasons like health or age. The types of NHL include Diffuse Large B-Cell Lymphoma and others.
• Scientific title: 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
• Date of first enrolment: 13/06/2011
• Target sample size: 377
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020147-12
• 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 Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Lithuania, Mexico, Netherlands, Poland, Portugal, Russian Federation, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

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 10to the power of 9/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.
9. 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.
10. All female and male subjects who are biologically capable of h
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.
11. Major surgery, not related to debulking surgical procedures, =28 days before first dose of investigational product
12. Chemotherapy, cancer immunosuppressive therapy, monoclonal antibodies including rituximab growth factors (except erythropoietin), or investigational drugs/devices =28 days before first dose of investigational product in this study. Subjects receiving high doses of corticosteroids must have been tapered to a stable dose at least 7 days before the first dose of investigational product. Patients must not receive a medication known to predispose to Torsades des Points within 7 days of first dose.
13. Pregnant or breastfeeding women.
14. Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.
15. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition).
16. Concurrent active malignancy other than nonmelanoma 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.
17. Primary effusion lymphoma, Burkitts, lymphoblastic, T-cell, indolent, and not otherwise specified lymphomas.
18. Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 50% or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure.
19. Previous myocardial infarction or symptomatic or clinically significant pulmonary hypertension =6 months before first dose of investigational product.
20. History of clinically significant ventricular arrhythmia, prolonged QTc interval, or unexplained syncope.
21. Screening QTcF interval >470 msec (based on the average of 3 consecutive ECGs).
22. History of chronic liver disease (eg, cirrhosis) or suspected history of alcohol abuse.
23. Administration of a live vaccine =6 weeks before first dose of investigational product.
24. Any major illness/condition or abnormal laboratory finding that, in the investigator’s judgment, will substantially increase the risk associated

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

Health Condition(s) or Problem(s) studied

Aggressive Non-Hodgkin Lymphoma (NHL)
MedDRA version: 15.1 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Inotuzumab Ozogamicin
Product Code: PF-05208773
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Inotuzumab ozogamicin
CAS Number: N/A
Current Sponsor code: PF-05208773
Other descriptive name: CMC-544
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: GEMZAR
Product Name: gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE HYDROCHLORIDE
CAS Number: 122111-03-9
Other descriptive name: gemcitabine hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: Ribomustin
Product Name: BENDAMUSTINE HYDROCHLORIDE
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 16506277
Other descriptive name: bendamustine hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Mabthera
Product Name: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: Rituximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Levact® 2.5 mg/ml powder for a concentrate to produce an infusion solution
Product Name: Bendamustine hydrochloride
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 3543-75-7
Other descriptive name: bendamustine hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 5 years

Primary end point(s): Overall survival (OS).

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

Secondary Objective: ? To evaluate the safety and tolerability of inotuzumab ozogamicin in combination with rituximab compared to the active comparator arm;
? To evaluate the efficacy of inotuzumab ozogamicin in combination with rituximab, as measured by overall (objective) response rate (ORR), progression free survival (PFS), and duration of response (DoR) compared to the active comparator arm;
? To compare patient-reported health-related quality of life (HRQOL), lymphoma
specific symptoms, and health status between the treatment arms.

Secondary Outcome(s)

Secondary end point(s): • Progression free survival (PFS);
• Overall (objective) response rate (ORR);
• Duration of response (DoR);
• Patient-reported health-related quality of life, lymphoma specific symptoms, and health status for subjects in each treatment arm as measured by the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) and EuroQol-5D (EQ 5D) questionnaires.

Timepoint(s) of evaluation of this end point: Approximately every 3 to 6 months

Secondary ID(s)

2010-020147-12-CZ

B1931008

Source(s) of Monetary Support

Pfizer