Title An Open-Label, Phase 1/2 Study of Inotuzumab Ozogamicin in subjects with relapsed or refractory CD22-Positive Accute Lymphocytic Leukemia
IRB PFIZ 1911
Hospital Main Campus
Phase Phase 1, Phase 2
Disease Leukemia, Acute Lymphoblastic (ALL)
Drug Inotuzumab Ozogamicin
- Part 1: Dose-Finding: To assess safety, tolerability and preliminary efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed/refractory adult ALL in order to select the recommended phase 2 dose (RP2D)/schedule.
- Part 2: Expansion Cohort: To further evaluate safety and efficacy at the RP2D/schedule.
- Part 3: Phase 2: To evaluate the efficacy of inotuzumab ozogamicin, as measured by the hematologic remission rate (CR + CRi) in patients in second or later salvage setting.
- To evaluate the overall safety profile.
- To evaluate the efficacy of inotuzumab ozogamicin, as measured by the hematologic response rate (CR + CRi + PR), durations of response (DoR) and remission (DoR1), progression free survival (PFS) and overall survival (OS);
- To characterize the pharmacokinetic profile of inotuzumab ozogamicin;
- To explore the pharmacodynamic effects of inotuzumab ozogamicin.
- To explore the pharmacogenomic effects of inotuzumab ozogamicin.
- Subjects with a diagnosis of CD22-positive ALL (ie, ≥20% blasts CD22-positive) based on local immunophenotyping and histopathology) who have:
- Refractory disease, defined as disease progression or no response while receiving their most recent prior anti-cancer therapy.
- Relapsed disease, defined as response to their most recent prior anti-cancer therapy with subsequent relapse.
- Phase 2: Subjects due to receive ≥ salvage 2 therapy.
- Subjects with lymphoblastic lymphoma with bone marrow involvement with ≥ 5% lymphoblasts are eligible.
- Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor.
- Age 18 years or older.
- ECOG performance status of 0 - 3.
- Adequate renal function, including serum creatinine ≤ 2 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 40 mL/min as calculated using the method standard for the institution.
- 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.
- Negative serum pregnancy test within 3 days before first treatment if the subject is a woman of childbearing potential. Sexually mature women are considered to be of childbearing potential if they have not undergone hysterectomy or have not been postmenopausal for at least 24 consecutive months. This includes women who are using contraceptives, or whose sexual partners are either sterile or using contraceptives.
- Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Provision of written informed consent indicating that the subject has been informed of all the pertinent aspects of the trial to be followed.
- Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedures.
- Subjects with isolated extramedullary relapse.
- Subjects with active central nervous system (CNS) leukemia. Assessment of CNSdisease (eg, by lumbar puncture) will be done in patients with symptoms suggestiveof CNS disease.
- Prior allogeneic hematopoietic stem cell transplant (HSCT) or otheranti-CD22 immunotherapy within ≤4 months before first dose of study treatment.Subjects must have completed immunosuppression therapy prior to enrollment. Atstudy entry, subjects must not have ≥ Grade 2 acute graft versus host disease (GvHD),or either moderate or severe limited chronic GvHD, or extensive chronic GvHD ofany severity.
- Prior monoclonal antibodies within ≤6 weeks before first dose of study treatment.
- Prior chemotherapy within ≤2 weeks before first dose of study treatment with the following exceptions:
- Steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine and thioguanine are permitted within 2 weeks of study start.
- Craniospinal radiation is prohibited. However, other concurrent therapy for CNS prophylaxis is permitted.
- Peripheral lymphoblasts > 25,000/µL. (Treatment with hydroxyurea is permitted within 2 weeks of the first dose of study treatment in order to reduce the white blood cell count).
- History of severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibody.
- 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).
- 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.
- Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).
- Evidence or history 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.
- Major surgery within ≤4 weeks before first dose of study treatment.
- Pregnant or breastfeeding women.
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition).
- 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.
- 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.
- Myocardial infarction ≤6 months before first dose of study treatment.
- History of clinically significant ventricular arrhythmia, prolonged QTc interval, or unexplained syncope not believed to be vasovagal in nature.
- Screening QTcF interval > 470 msec (based on the average of 3 consecutive ECGs).
- History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.
- Administration of live vaccine ≤6 weeks before first dose of study treatment.
- 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.
- Current active treatment in another clinical study.
- Subjects previously randomized to Pfizer-sponsored clinical trial B1931022 (clintrials.gov identifier NCT01564784).
- Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.