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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02641002
• Other study ID #: CC-90002-AML-001
• Status: Terminated
• Phase: Phase 1
• Start date: March 1, 2016
• Est. completion date: July 18, 2018

Study information

• Verified date: October 2018
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: July 18, 2018
• Est. primary completion date: July 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• CC-90002
Monoclonal Ab to CD47

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	UCLA Division of Hematology Oncology	Los Angeles	California
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mayo Clinic Phoenix	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting Toxicity (DLT)	Number of participants with a DLT	Up to 26 months
Primary	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
Primary	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	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
Secondary	Pharmacokinetics-Cmax	Maximum observed concentration in serum	Up to 35 months
Secondary	Pharmacokinetics-AUC	Area under the serum concentration - time curve	Up to 35 months
Secondary	Pharmacokinetics-Tmax	Time to peak (maximum) serum concentration	Up to 35 months
Secondary	Pharmacokinetics-T 1/2	Terminal half-life (T 1/2)	Up to 35 months
Secondary	Pharmacokinetics- CL	Total body clearance of the drug from the serum	Up to 35 months
Secondary	Pharmacokinetics- Vss	Volume of distribution at steady-state	Up to 35 months
Secondary	Anti-Drug Antibodies (ADAs)	Determine the presence and frequency of anti-drug antibodies	Up to 35 months