Phase 3 Study of Inotuzumab Ozogamicin versus Investigator's Choice of Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

• Register: EUCTR
• Last refreshed on: 23 May 2022
• Main ID: EUCTR2011-005491-41-BE
• Date of registration: 28/10/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 10017
• Public title: Phase 3 Study of Inotuzumab Ozogamicin versus Investigator's Choice of Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia
• Scientific title: An Open-label, Randomized Phase 3 Study of Inotuzumab Ozogamicin Compared to a Defined Investigator’s Choice in Adult Patients with Relapsed or Refractory CD22-Positive Acute Lymphoblastic Leukemia (ALL)
• Date of first enrolment: 13/03/2014
• Target sample size: 325
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005491-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, Croatia, Czech Republic, Finland, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Serbia, Singapore, Slovakia, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1.Relapsed or refractory CD22-positive ALL (= 5% marrow blasts, assessed by morphology; ie, M2 or M3 marrow) due to receive either salvage 1 or salvage 2 therapy and for which either arm of randomized study therapy offers a reasonable treatment option;
2.Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi-agent induction chemotherapy;
3.Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
4.Patients with lymphoblastic lymphoma and bone marrow involvement =5% lymphoblasts by morphologic assessment;
5.Age 18 years or older;
6.ECOG performance status 0-2;
7.Adequate liver function, including total serum bilirubin =1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) =2.5 x ULN. If organ function abnormalities are considered due to tumor, total serum bilirubin must be =2 x ULN and AST/ALT =2.5 x ULN;
8.Serum creatinine =1.5 x upper limit of normal (ULN) or any serum creatinine level associated with a measured or calculated creatinine clearance of =40 mL/min;
9.Male and female patients of childbearing potential and at risk of pregnancy must agree to use a highly effective method of contraception throughout the study and for a minimum of 90 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (i.e., meet at least one of the following criteria):
a. Have undergone hysterectomy or bilateral oophorectomy; or
b. Have medically confirmed ovarian failure; or
c. Are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause.
10.Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study; patients with mental capacity which requires the presence of a legally authorized representative will be excluded from the study.
11.Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
1.Isolated extramedullary relapse (i.e., testicular or CNS);
2.Burkitt’s or mixed phenotype acute leukemia based on the WHO 2008 criteria;
3.Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion;
4.Prior chemotherapy within 2 weeks before randomization with the following exceptions:
a. To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine;
b. For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors.
Patients must have recovered from acute non hematologic toxicity (to = Grade 1) of all previous therapy prior to enrollment;
5.Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization;
6.Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy = 4 months before randomization. Patients must have completed immunosuppression therapy for treatment of GvHD prior to enrollment. At randomization, patients must not have = Grade 2 acute GvHD, or extensive chronic GvHD;
7.Peripheral absolute lymphoblast count =10,000 /µL (treatment with hydroxyurea and/or steroids/vincristine is permitted within 2 weeks of randomization to reduce the WBC count);
8.Known systemic vasculitides (eg, Wegener’s granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as HIV infection or severe inflammatory disease);
9.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;
10.Major surgery within = 4 weeks before randomization;
11.Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);
12.Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for =2 years;
13.Cardiac function, as measured by left ventricular ejection fraction (LVEF) that is less than 45%, or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;
14.Patients with active heart disease (NYHA class =3 as assessed by history and physical examination);
15.QTcF >470 msec (based on the average of 3 consecutive ECGs);
16.Myocardial infarction =6 months before randomization;
17.History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of AV block unless a permanent pacemaker has been implanted;
18.Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia);
19.History of chronic liver disease (eg, cirrhosis) or su

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

Health Condition(s) or Problem(s) studied

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

Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia

Intervention(s)

Product Name: Inotuzumab Ozogamicin
Product Code: PF-05208773
Pharmaceutical Form: Powder for concentrate for solution for infusion
CAS Number: N/A
Current Sponsor code: CMC-544
Other descriptive name: inotuzumab ozogamicin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1 or 4-

Trade Name: CYTOSAR, 500mg, powder and solvent for solution for injection
Product Name: Cytarabine 500 mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Other descriptive name: cytarabine 500mg powder for solution for infusion
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: CYTOSAR 1 g
Product Name: Cytarabine 1 g
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: CYTARABINE
CAS Number: 147-94-4
Other descriptive name: cytarabine 1 gram powder for solution for infusion
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Neupogen 600 µg/ml
Product Name: Filgrastim
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: FILGRASTIM
CAS Number: 121181-53-1
Other descriptive name: filgrastim 300 µg (600 µg/ml) solution for injection in a prefilled syringe
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 600-

Trade Name: Neupogen 960 µg/ml
Product Name: Filgrastim
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: FILGRASTIM
CAS Number: 121181-53-1
Other descriptive name: filgrastim 480 µg (960 µg /ml) solution for injection in a prefilled syringe
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 960-

Trade Name: Fludarabine Actavis 50 mg
Product Name: Fl

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Dependent on individual patient response

Main Objective: To compare the hematological remission, defined as CR (both CR and CRi), as reported by the external independent endpoint adjudication committee, in patients with relapsed/refractory ALL randomized to receive inotuzumab ozogamicin (Arm A) versus patients randomized to receive active comparator (Arm B).

Primary end point(s): • CR and CRi.

Secondary Objective: Safety and efficacy endpoints will be compared between the inotuzumab ozogamicin arm and the active comparator arm and will include:

Key Secondary Objective:
• To compare the overall survival of patients with relapsed/refractory ALL.
Other Secondary Objectives:
• To compare the duration of response;
• To compare the progression-free survival;
• To compare the rate of stem-cell transplantation in patients;
• To characterize the safety and tolerability including the rate of VOD (veno-occlusive disease)/SOS (sinusoidal obstruction syndrome) following allogeneic stem cell transplant;
• To assess minimal residual disease levels and cytogenetics in patients achieving a CR/CRi;
• To determine the population pharmacokinetic parameters of inotuzumab ozogamicin and confirm sources of exposure variability;
• To compare patient-reported health-related quality of life (HRQOL) and patient-reported health status between treatment arms.

Secondary Outcome(s)

Secondary end point(s): • OS (Key secondary endpoint);
• DoR;
• PFS;
• Number of Transplants;
• Adverse events and laboratory abnormalities (CTCAE v3.0 grade, timing, seriousness and relatedness);
• MRD and cytogenetics in responding patients;
• PK;
• EORTC QLQ-C30 and EQ-5D.

Timepoint(s) of evaluation of this end point: Dependent on individual patient response

Secondary ID(s)

2011-005491-41-HU

B1931022

Source(s) of Monetary Support

Pfizer Inc.

Ethics review

Status: Approved
Approval date: 13/03/2014
Contact:

Results

• Results available: Yes
• Date Posted: 23/03/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005491-41/results