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

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

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.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • California
    • Los Angeles, California, United States, 90095-1752
      • UCLA Division of Hematology Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women ≥ 18 years of age, at the time of signing the informed consent form (ICF).
2. 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.
3. Subject consents to hospitalization for first (Cycle 1 Day 1) dose of CC-90002 and for 72 hours after.
4. Subject consents to serial bone marrow aspiration and biopsies as specified.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
6. Eligible study subjects must exhibit acceptable liver, renal, and coagulation function as assessed by laboratory tests.
7. 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:

1. Active central nervous system (CNS) leukemia or known CNS leukemia.
2. Immediately life-threatening, severe complications of leukemia.
3. Impaired cardiac function or clinically significant cardiac diseases.
4. Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
5. Prior autologous hematopoietic stem cell transplant ≤ 3 months.
6. Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months.
7. Systemic immunosuppressive therapy post HSCT or with clinically significant graft-versus-host disease (GVHD).
8. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks whichever is shorter.
9. Major surgery ≤ 2 weeks and recovered from any clinically significant effects of recent surgery.
10. Pregnant or nursing females.
11. Known HIV infection.
12. Known chronic hepatitis B or C (HBV/HCV) infection.
13. Ongoing treatment with chronic, therapeutic dosing of anti-coagulants.
14. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
15. History of concurrent second cancers requiring active, ongoing systemic treatment.
16. Subjects for whom potentially curative anticancer therapy is available.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Michael Burgess, MD, PhD, Celgene Corporation

Publications and helpful links

General Publications

• Narla RK, Modi H, Bauer D, Abbasian M, Leisten J, Piccotti JR, Kopytek S, Eckelman BP, Deveraux Q, Timmer J, Zhu D, Wong L, Escoubet L, Raymon HK, Hariharan K. Modulation of CD47-SIRPalpha innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody. Cancer Immunol Immunother. 2022 Feb;71(2):473-489. doi: 10.1007/s00262-021-03010-6. Epub 2021 Jul 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): July 18, 2018
• Study Completion (Actual): July 18, 2018

Study Registration Dates

• First Submitted: November 12, 2015
• First Submitted That Met QC Criteria: December 22, 2015
• First Posted (Estimate): December 29, 2015

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; Antibody; MDS; Hematologic Cancers; Myelodysplastic syndrome; CD47; Monoclonal; Blood disorder; CC-90002
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: CC-90002-AML-001