Ensayos clínicos

Inclusion Criteria:

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject is ≥ 18 years of age at the time of signing the ICF.
• Relapsed or refractory CD33 positive AML at last visit by local assessment as defined by the World Health Organization (WHO) Classification who have failed or who are ineligible for or have refused all available therapies for AML which may provide clinical benefit.
• Subjects who have received prior treatment with a CD33-targeted therapy may be included in the study. 6. Subject has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion without conditioning.
• Subjects must have the following screening laboratory values:
  • Total White Blood Cell count (WBC) < 25 x 10^9 /L prior to first infusion. Treatment with hydroxyurea to achieve this level is allowed;
  • Potassium, calcium (corrected Ca or free [ionized] Ca), and magnesium within normal limits or correctable with supplements;
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be ≤ 5.0 x ULN;
  • Uric acid ≤ 7.5 mg/dL (446 μmol/L). Prior and/or concurrent treatment with hypouricemic agents (e.g., allopurinol, rasburicase) are allowed;
  • Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome (e.g., a gene mutation in UGT1A1), in which case serum total bilirubin must be ≤ 3.0 mg/dL;
  • Estimated serum creatinine clearance of ≥ 50 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated;
  • International normalized ratio (INR) < 1.5 x ULN and aPTT < 1.5 x ULN (for subjects not receiving therapeutic anticoagulation);
  • Platelets (plts) ≥ 15,000/µL with transfusions allowed;
  • Hemoglobin (Hgb) ≥ 7 g/dL with transfusions allowed.
• Females of childbearing potential (FCBP)* must:
  • Either commit to true abstinence** from heterosexual contact or agree to use, and be able to comply with, at least one highly effective method of contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; or vasectomized partner), from signing the ICF, throughout the study, including during dose interruptions, and for at least 105 days following the last dose of CC-96191. The selected contraceptive method will be reviewed and evaluated on a monthly basis, and this will be noted in source documents; and
  • Have two negative pregnancy tests as verified by the Investigator prior to starting CC-96191. She must agree to ongoing pregnancy testing during the course of the study, through 105 days following treatment discontinuation. This applies even if the subject practices true abstinenceb from heterosexual contact. The subject may not receive IP until the Investigator has verified that the result of the pregnancy test is negative;
  • Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at Screening;
  • Have a negative serum or urine pregnancy test (Investigator’s discretion) within 72 hours prior to the first dose (Cycle 1 Day 1) of study treatment, and within 72 hours prior to Day 1 of every subsequent cycle (note that the Screening serum pregnancy test can be used as the test prior to Day 1 study treatment if it is performed within the prior 72 hours). A serum or urine pregnancy test (investigators discretion) must also be performed at treatment discontinuation and at 105 days following treatment discontinuation;
  • Avoid conceiving for 105 days after the last dose of CC-96191;
  • Agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinenceb from heterosexual contact.
• Males must practice true abstinence** (which must be reviewed, evaluated and source documented on a monthly basis) or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or a FCBP and will avoid conceiving from signing the ICF, while participating in the study, during dose interruptions, and for at least 105 days following CC-96191 discontinuation, even if he has undergone a successful vasectomy. *A female of childbearing potential is a sexually mature woman who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months).
• **True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception].

Exclusion Criteria:

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Subject has any condition; e.g., active or uncontrolled infection, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Subjects with previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1:
  • Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the subject at a higher risk of receiving study treatment.
• Previous SARS-CoV-2 vaccine within 14 days of C1D1. For vaccines requiring more than one dose, the full series (e.g., both doses of a two-dose series) should be completed by at least 14 days prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject at risk.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject is suspected or proven to have acute promyelocytic leukemia (FAB M3) based on morphology, immunophenotype, molecular assay, or karyotype.
• Subject has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment. Hydroxyurea is allowed to control peripheral leukemia blasts.
• Subjects with prior autologous hematopoietic stem cell transplant who, in the investigator’s judgment, have not fully recovered from the effects of the last transplant (e.g., transplant-related side effects).
• Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing.
• Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted.
• Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2.
• Subject has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening.
• Subject has immediate life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. The subject should be afebrile for at least 72 hours.
• History of concurrent second cancers requiring active, ongoing systemic treatment.
• Subject is known seropositive or active infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus.
• Subject with a positive SARS-CoV-2 test during Screening will be required to delay dosing for a minimum of 10 days from the last positive test or resolution of symptoms, whichever is longer.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
  • Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO);
  • Complete left bundle branch or bifascicular block;
  • Congenital long QT syndrome;
  • Persistent or clinically meaningful ventricular arrhythmias;
  • QT interval with Fridericia’s correction (QTcF) ≥ 470 msec on Screening electrocardiogram (ECG) (mean of triplicate recordings);
  • Unstable angina or myocardial infarction ≤ 3 months prior to starting CC-96191;
  • Congestive heart failure (New York Heart Association Class III or IV) ≤ 12 months prior to the first dose of CC-96191.
• Subject is a pregnant or lactating female.
• Prior live virus vaccines within at least 4 weeks prior to starting study drug.
• Subject has known or suspected hypersensitivity to any of the components or any of the excipients of the study treatment.

Eligibility last updated 2/7/22. Questions regarding updates should be directed to the study team contact.