A Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)
- Conditions
- Leukemia, Myeloid, AcuteMyelodysplastic Syndromes
- Interventions
- Registration Number
- NCT02641002
- Lead Sponsor
- Celgene
- Brief Summary
Study CC-90002-AML-001 is an open-label, Phase 1 dose escalation (Part A) and expansion (Part B), clinical study of CC-90002, administered by intravenous (IV) infusion, in subjects with relapsed and/or primary refractory AML and high-risk MDS. The study will explore escalating doses of CC-90002 using a 3 + 3 dose escalation design in Part A, followed by dose expansion in Part B.
The primary objective is to determine the safety and tolerability of CC-90002 and also to define the non-tolerated dose (NTD), the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of CC-90002.
- Detailed Description
In both Part A and Part B, treatments will be administered in two phases starting with an induction phase followed by a maintenance phase. During the induction phase, treatments will be administered in 42-day cycles in Cycles 1 through 4. Following completion of Cycle 4 in the induction phase, subjects with non-progressive disease will enter the maintenance phase. During the maintenance phase, treatments will be administered in 28 day cycles. Subjects may continue CC-90002 for up to a maximum of 2 years (eg, induction phase Cycles 1 through 4 and maintenance phase Cycles 5 through 24) or until clinically significant disease progression, the occurrence of intolerable toxicity, or physician/subject decision to discontinue CC-90002, whichever comes first.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 28
- Men and women ≥ 18 years of age, at the time of signing the informed consent form (ICF).
- Relapsed and/or primary refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) with subtype refractory anemia with excess blasts (RAEB)-2 defined as high or very high-risk that is recurrent or refractory, or the patient is intolerant to established therapy.
- Subject consents to hospitalization for first (Cycle 1 Day 1) dose of CC-90002 and for 72 hours after.
- Subject consents to serial bone marrow aspiration and biopsies as specified.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
- Eligible study subjects must exhibit acceptable liver, renal, and coagulation function as assessed by laboratory tests.
- Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and for up to 8 weeks following the last dose of CC 90002.
- Active central nervous system (CNS) leukemia or known CNS leukemia.
- Immediately life-threatening, severe complications of leukemia.
- Impaired cardiac function or clinically significant cardiac diseases.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Prior autologous hematopoietic stem cell transplant ≤ 3 months.
- Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months.
- Systemic immunosuppressive therapy post HSCT or with clinically significant graft-versus-host disease (GVHD).
- Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks whichever is shorter.
- Major surgery ≤ 2 weeks and recovered from any clinically significant effects of recent surgery.
- Pregnant or nursing females.
- Known HIV infection.
- Known chronic hepatitis B or C (HBV/HCV) infection.
- Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
- History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
- History of concurrent second cancers requiring active, ongoing systemic treatment.
- Subjects for whom potentially curative anticancer therapy is available.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose escalation of CC-90002 CC-90002 CC-90002 by intravenous (IV) infusion on a 28 day cycle
- Primary Outcome Measures
Name Time Method Dose-limiting Toxicity (DLT) Up to 26 months Number of participants with a DLT
Non-tolerated Dose (NTD) Up to 26 months The NTD is defined as the dose at which 2 or more of up to 6 evaluable subjects in a cohort experience a DLT in Cycle 1
Maximum tolerated dose (MTD) Up to 26 months The MTD is defined as the last dose level(s) below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during Cycle 1.
- Secondary Outcome Measures
Name Time Method Preliminary Efficacy of CC-90002 Up to 35 months Determined by response rates of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by disease-appropriate response criteria.
Pharmacokinetics-Cmax Up to 35 months Maximum observed concentration in serum
Pharmacokinetics-AUC Up to 35 months Area under the serum concentration - time curve
Pharmacokinetics-Tmax Up to 35 months Time to peak (maximum) serum concentration
Pharmacokinetics-T 1/2 Up to 35 months Terminal half-life (T 1/2)
Pharmacokinetics- CL Up to 35 months Total body clearance of the drug from the serum
Pharmacokinetics- Vss Up to 35 months Volume of distribution at steady-state
Anti-Drug Antibodies (ADAs) Up to 35 months Determine the presence and frequency of anti-drug antibodies
Trial Locations
- Locations (6)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic Phoenix
🇺🇸Phoenix, Arizona, United States
UCLA Division of Hematology Oncology
🇺🇸Los Angeles, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
University of Chicago
🇺🇸Chicago, Illinois, United States