A Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Open-label, Dose Finding Study of CC-90002, a Monoclonal Antibody Directed Against CD47, in Subjects With Acute Myeloid Leukemia and High-Risk Myelodsplastic Syndrome

Conditions
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Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: CC-90002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation of CC-90002<br>CC-90002 by intravenous (IV) infusion on a 28 day cycle | Drug: CC-90002<br>* Monoclonal Ab to CD47<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicity (DLT) | Number of participants with a DLT | Up to 26 months | 
| Non-tolerated Dose (NTD) | 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 | Up to 26 months | 
| Maximum tolerated dose (MTD) | 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. | Up to 26 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary Efficacy of CC-90002 | Determined by response rates of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by disease-appropriate response criteria. | Up to 35 months | 
| Pharmacokinetics-Cmax | Maximum observed concentration in serum | Up to 35 months | 
| Pharmacokinetics-AUC | Area under the serum concentration - time curve | Up to 35 months | 
| Pharmacokinetics-Tmax | Time to peak (maximum) serum concentration | Up to 35 months | 
| Pharmacokinetics-T 1/2 | Terminal half-life (T 1/2) | Up to 35 months | 
| Pharmacokinetics- CL | Total body clearance of the drug from the serum | Up to 35 months | 
| Pharmacokinetics- Vss | Volume of distribution at steady-state | Up to 35 months | 
| Anti-Drug Antibodies (ADAs) | Determine the presence and frequency of anti-drug antibodies | Up to 35 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-90002, Monoclonal, Antibody, CD47, Hematologic Cancers, Acute Myeloid Leukemia, AML, Myelodysplastic syndrome, MDS, Blood disorder