A Dose-finding Study of CC-90009 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-risk Myelodysplastic Syndromes

Sponsor

Celgene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02848001

Collaborator

(none)

162

Enrollment

Locations

Arms

106.4

Anticipated Duration (Months)

6.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

CC-90009-AML-001 is a phase 1, open-label, dose escalation and expansion, study in subjects with relapsed or refractory acute myeloid leukemia and relapsed or refractory higher-risk myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes	Drug: CC-90009	Phase 1

Detailed Description

Study CC-90009-AML-001 is an open-label, Phase 1, dose escalation and expansion, first-in-human clinical study of CC-90009 in subjects with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory higher-risk myelodysplastic syndrome.

The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-90009 in relapsed and refractory AML. The expansion part, (Part B), will further evaluate the safety and efficacy of CC-90009 administered at or below the maximum tolerated dose (MTD) in selected expansion cohorts of one or more dosing regimens in order to determine the recommended Phase 2 dose (RP2D) for subjects with relapsed or refractory AML and relapsed or refractory higher-risk myelodysplastic syndrome.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

162 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-label, Dose Finding Study of CC-90009, a Novel Cereblon E3 Ligase Modulating Drug, in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes

Actual Study Start Date :

Nov 14, 2016

Anticipated Primary Completion Date :

Sep 25, 2024

Anticipated Study Completion Date :

Sep 26, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-90009 - Part A Will be administered intravenously per dosing schedule in a 28-day cycle.	Drug: CC-90009 CC-90009
Experimental: CC-90009 - Part B - AML and MDS patients Relapsed or refractory AML and MDS subjects. IP will be administered intravenously per dosing schedule determined in Part A	Drug: CC-90009 CC-90009

Arm

Intervention/Treatment

Experimental: CC-90009 - Part A

Will be administered intravenously per dosing schedule in a 28-day cycle.

Drug: CC-90009

CC-90009

Experimental: CC-90009 - Part B - AML and MDS patients

Relapsed or refractory AML and MDS subjects. IP will be administered intravenously per dosing schedule determined in Part A

Drug: CC-90009

CC-90009

Outcome Measures

Primary Outcome Measures

Dose- limiting toxicity (DLT) [Up to 42 days]
Number of participants with a DLT
Non-tolerated dose (NTD) [Up to 42 days]
Dose level at which 2 or more of up to 6 evaluable subjects in any dose cohort experience a DLT in Cycle 1 during dose escalation.
Maximum tolerated dose (MTD) [Up to 42 days]
Last dose level(s) below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT in Cycle 1 during dose escalation
Number of participants with Adverse Events (AEs) [Up to 42 days]
Number of participants with laboratory abnormalities [Up to 42 days]
Number of participants with vital sign abnormalities [Up to 42 days]
Number of participants with electrocardiogram (ECG) abnormalities [Up to 42 days]
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities [Up to 42 days]
Number of participants with Left Ventricle Ejection Fraction (LVEF) assessment abnormalities [Up to 42 days]
Number of participants with physical examination abnormalities [Up to 42 days]

Secondary Outcome Measures

Preliminary efficacy of CC-90009 - acute myeloid leukemia (AML) [Up to 2.5 years]
Determined by response rates of AML by disease response criteria
Overall survival [Up to 2.5 years]
Relapse-free survival [Up to 2.5 years]
Progression-free survival [Up to 2.5 years]
Event-free survival [Up to 2.5 years]
Duration of remission [Up to 2.5 years]
Duration of response [Up to 2.5 years]
Time to remission for AML participants [Up to 2.5 years]
Time to response for AML participants [Up to 2.5 years]
Preliminary efficacy of CC-90009 - Higher-risk myelodysplastic syndromes (HR-MDS) [Up to 2.5 years]
Determined by response rates of HR-MDS by disease response criteria
Time to AML transformation [Up to 2.5 years]
Time to remission for HR-MDS participants [Up to 2.5 years]
Time to response for HR-MDS participants [Up to 2.5 years]
Pharmacokinetics-Cmax [Up to Day 11]
Maximum observed concentration in plasma
Pharmacokinetics - AUC24 [Up to Day 11]
Area under the plasma concentration time-curve from time 0 to 24 hours
Pharmacokinetics - tmax [Up to Day 11]
Time to peak (maximum) plasma concentration
Pharmacokinetics - t 1/2 [Up to Day 11]
terminal half-life
Pharmacokinetics - CL [Up to Day 11]
Total body clearance of the drug from plasma
Pharmacokinetics - Vss [Up to Day 11]
Volume of distribution at steady-state

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 ICD (Informed Consent Document).
Subject must understand and voluntarily sign an ICD prior to any study-related assessments/procedures being conducted.
Relapsed or refractory AML (Acute Myeloid Leukemia) (Parts A and B) or relapsed or refractory (R/R) higher-risk MDS (Myelodysplastic Syndrome) (HR-MDS) (Part B only) as defined by World Health Organization criteria who are not suitable for other established therapies.
In Part A, R/R AML
In Part B, R/R AML including

Relapsed after allogeneic HSCT or
In second or later relapse or
Refractory to initial induction or re-induction treatment or
Refractory or relapse after HMA treatment (HMA failure defined as primary progression or lack of clinical benefit after a minimum of 6 cycles or unable to tolerate HMA due to toxicity) or
Refractory within 1 year of initial treatment (excluding those with favorable risk based on cytogenetics)

In Part B, R/R HR-MDS (Revised International Prognostic Scoring System score (IPSS-R) > 3.5 points, IPSS-R calculated during screening period):

IPSS-R intermediate risk (in combination with more than 10% bone marrow blasts or poor or very poor IPSS-R cytogenetic risk) or
IPSS-R high or
IPSS-R very high risk

Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.
At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion (DLI) without conditioning.
Subjects must have the following screening laboratory values:

Corrected serum Ca or free (ionized) serum Ca within normal limits (WNL).

o Corrected Ca (mg/dL) = Total Ca (mg/dL) - 0.8 (albumin [g/dL] - 4)

Total White Blood Cell count (WBC) < 25 x 10^9/L prior to first infusion. Prior or concurrent treatment with hydroxyurea to achieve this level is allowed.
Potassium and magnesium within normal limits or correctable with supplements.
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamate pyruvic transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN).
Uric acid ≤ 7.5 mg/dL (446 μmol/L). Prior and/or concurrent treatment with hypouricemic agents (eg, allopurinol, rasburicase) are allowed.
Selected electrolytes within normal limits or correctable with supplements.
Serum bilirubin ≤ 1.5 x ULN (upper limit of normal).
Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
International normalized ratio (INR) < 1.5 x ULN and Partial thromboplastin time (PTT) < 1.5 x ULN.

Exclusion Criteria:

Subjects with acute promyelocytic leukemia (APL)
Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is clinical suspicion of CNS involvement by leukemia during screening.
Patients with prior autologous hematopoietic stem cell transplant who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (e.g., transplant related side effects).
Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-90009.
Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD).
Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting CC-90009, whichever is shorter. Hydroxyurea is allowed to control peripheral leukemia blasts.
Leukapheresis ≤ 2 weeks prior to starting CC-90009.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06510
2	Yale Cancer Center	New Haven	Connecticut	United States	06510
3	Northwestern Memorial	Chicago	Illinois	United States	60611
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Washington University Siteman Cancer Center	Saint Louis	Missouri	United States	63110
6	Washington University Siteman Cancer Center	Saint Louis	Missouri	United States	63110
7	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
8	Princess Margaret Hospital University Health Network	Toronto	Ontario	Canada	M5G 2M9
9	Institut Paoli Calmettes	Marseille Cedex 9		France	13273
10	Hopital Lyon Sud	Pierre Benite		France	69310
11	Institut Claudius Regaud, IUCT-Oncopole	Toulouse		France	31059
12	Haukeland University Hospital	Bergen		Norway	N-5053
13	Oslo University Hospital, Rikshospitalet HF	Oslo		Norway	N-0027
14	Hospital Germans Trias I Pujol	Badalona		Spain	8916
15	Local Institution - 603	Badalona		Spain	8916
16	H Clinic I Provincial	Barcelona		Spain	08036
17	Local Institution - 602	Barcelona		Spain	08036
18	MD Anderson Cancer Center - Madrid	Madrid		Spain	28033
19	Clinica Universidad de Navarra	Pamplona		Spain	31008
20	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
21	Hosptial La Fe	Valencia		Spain	46009
22	Clatterbridge Cancer Centre - Liverpool	Liverpool		United Kingdom	L9 7BA
23	Local Institution - 301	Oxford		United Kingdom	0X3 7LE
24	The Churchill Hospital	Oxford		United Kingdom	0X3 7LE