Back to resultsA Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)
Primary Purpose
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CC-90002
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring CC-90002, Monoclonal, Antibody, CD47, Hematologic Cancers, Acute Myeloid Leukemia, AML, Myelodysplastic syndrome, MDS, Blood disorder
Eligibility Criteria
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.
Sites / Locations
- Mayo Clinic Phoenix
- UCLA Division of Hematology Oncology
- Yale Cancer Center
- University of Chicago
- Dana-Farber Cancer Institute
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dose escalation of CC-90002
Arm Description
CC-90002 by intravenous (IV) infusion on a 28 day cycle
Outcomes
Primary Outcome Measures
Dose-limiting Toxicity (DLT)
Number of participants with a DLT
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
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.
Secondary Outcome Measures
Preliminary Efficacy of CC-90002
Determined by response rates of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by disease-appropriate response criteria.
Pharmacokinetics-Cmax
Maximum observed concentration in serum
Pharmacokinetics-AUC
Area under the serum concentration - time curve
Pharmacokinetics-Tmax
Time to peak (maximum) serum concentration
Pharmacokinetics-T 1/2
Terminal half-life (T 1/2)
Pharmacokinetics- CL
Total body clearance of the drug from the serum
Pharmacokinetics- Vss
Volume of distribution at steady-state
Anti-Drug Antibodies (ADAs)
Determine the presence and frequency of anti-drug antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02641002
Brief Title
A Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
Preliminary monotherapy data in relapsed/refractory AML and high-risk MDS did not offer a sufficiently encouraging profile for further dose escalation/expansion
Study Start Date
March 1, 2016 (Actual)
Primary Completion Date
July 18, 2018 (Actual)
Study Completion Date
July 18, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
Keywords
CC-90002, Monoclonal, Antibody, CD47, Hematologic Cancers, Acute Myeloid Leukemia, AML, Myelodysplastic syndrome, MDS, Blood disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose escalation of CC-90002
Arm Type
Experimental
Arm Description
CC-90002 by intravenous (IV) infusion on a 28 day cycle
Intervention Type
Drug
Intervention Name(s)
CC-90002
Intervention Description
Monoclonal Ab to CD47
Primary Outcome Measure Information:
Title
Dose-limiting Toxicity (DLT)
Description
Number of participants with a DLT
Time Frame
Up to 26 months
Title
Non-tolerated Dose (NTD)
Description
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
Time Frame
Up to 26 months
Title
Maximum tolerated dose (MTD)
Description
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.
Time Frame
Up to 26 months
Secondary Outcome Measure Information:
Title
Preliminary Efficacy of CC-90002
Description
Determined by response rates of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) by disease-appropriate response criteria.
Time Frame
Up to 35 months
Title
Pharmacokinetics-Cmax
Description
Maximum observed concentration in serum
Time Frame
Up to 35 months
Title
Pharmacokinetics-AUC
Description
Area under the serum concentration - time curve
Time Frame
Up to 35 months
Title
Pharmacokinetics-Tmax
Description
Time to peak (maximum) serum concentration
Time Frame
Up to 35 months
Title
Pharmacokinetics-T 1/2
Description
Terminal half-life (T 1/2)
Time Frame
Up to 35 months
Title
Pharmacokinetics- CL
Description
Total body clearance of the drug from the serum
Time Frame
Up to 35 months
Title
Pharmacokinetics- Vss
Description
Volume of distribution at steady-state
Time Frame
Up to 35 months
Title
Anti-Drug Antibodies (ADAs)
Description
Determine the presence and frequency of anti-drug antibodies
Time Frame
Up to 35 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Burgess, MD, PhD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
UCLA Division of Hematology Oncology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1752
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34247273
Citation
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.
Results Reference
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A Study of CC-90002 in Subjects With Acute Myeloid Leukemia (AML) and High-risk Myelodysplastic Syndrome (MDS)
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