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

Sponsor

Celgene (Industry)

Overall Status

Terminated

CT.gov ID

NCT02641002

Collaborator

(none)

Enrollment

Locations

Arm

28.6

Actual Duration (Months)

4.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes	Drug: CC-90002	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2016

Actual Primary Completion Date :

Jul 18, 2018

Actual Study Completion Date :

Jul 18, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Dose escalation of CC-90002

CC-90002 by intravenous (IV) infusion on a 28 day cycle

Drug: CC-90002

Monoclonal Ab to CD47

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Phoenix	Phoenix	Arizona	United States	85054
2	UCLA Division of Hematology Oncology	Los Angeles	California	United States	90095-1752
3	Yale Cancer Center	New Haven	Connecticut	United States	06510
4	University of Chicago	Chicago	Illinois	United States	60637
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021