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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02848001
• Other study ID #: CC-90009-AML-001
• Secondary ID: 2017-001535-39
• Status: Terminated
• Phase: Phase 1
• Start date: November 14, 2016
• Est. completion date: April 11, 2024

Study information

• Verified date: May 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 101
• Est. completion date: April 11, 2024
• Est. primary completion date: April 11, 2023
• 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 ICD (Informed Consent Document).

2. Subject must understand and voluntarily sign an ICD prior to any study-related assessments/procedures being conducted.

3. 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.

1. In Part A, R/R AML

2. 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)

3. 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

4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.

5. At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion (DLI) without conditioning.

6. 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:

1. Subjects with acute promyelocytic leukemia (APL)

2. 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.

3. 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).

4. Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning = 6 months prior to starting CC-90009.

5. Subjects on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD).

6. 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.

7. Leukapheresis = 2 weeks prior to starting CC-90009.

Related Conditions & MeSH terms

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

Intervention

Drug:
• CC-90009
CC-90009

Locations

Country	Name	City	State
Canada	Local Institution - 201	Toronto	Ontario
France	Local Institution - 505	Lillie Cedex
France	Institut Paoli Calmettes	Marseille Cedex 9
France	Hopital Lyon Sud	Pierre Benite
France	Local Institution - 502	Toulouse
Norway	Local Institution - 700	Bergen
Norway	Local Institution - 701	Oslo
Spain	Local Institution - 603	Badalona
Spain	Local Institution - 602	Barcelona
Spain	Local Institution - 604	Madrid
Spain	Local Institution - 605	Pamplona
Spain	Local Institution - 601	Salamanca
Spain	Local Institution - 600	Valencia
United Kingdom	Local Institution - 301	Oxford
United States	Local Institution - 103	Boston	Massachusetts
United States	Local Institution - 102	Chicago	Illinois
United States	Local Institution - 104	Hackensack	New Jersey
United States	Local Institution - 105	New Haven	Connecticut
United States	Local Institution - 101	Saint Louis	Missouri
United States	Stanford Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose- limiting toxicity (DLT)	Number of participants with a DLT	Up to 42 days
Primary	Non-tolerated dose (NTD)	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.	Up to 42 days
Primary	Maximum tolerated dose (MTD)	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	Up to 42 days
Primary	Number of participants with Adverse Events (AEs)		Up to 42 days
Primary	Number of participants with laboratory abnormalities		Up to 42 days
Primary	Number of participants with vital sign abnormalities		Up to 42 days
Primary	Number of participants with electrocardiogram (ECG) abnormalities		Up to 42 days
Primary	Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities		Up to 42 days
Primary	Number of participants with Left Ventricle Ejection Fraction (LVEF) assessment abnormalities		Up to 42 days
Primary	Number of participants with physical examination abnormalities		Up to 42 days
Secondary	Preliminary efficacy of CC-90009 - acute myeloid leukemia (AML)	Determined by response rates of AML by disease response criteria	Up to 2.5 years
Secondary	Overall survival		Up to 2.5 years
Secondary	Relapse-free survival		Up to 2.5 years
Secondary	Progression-free survival		Up to 2.5 years
Secondary	Event-free survival		Up to 2.5 years
Secondary	Duration of remission		Up to 2.5 years
Secondary	Duration of response		Up to 2.5 years
Secondary	Time to remission for AML participants		Up to 2.5 years
Secondary	Time to response for AML participants		Up to 2.5 years
Secondary	Preliminary efficacy of CC-90009 - Higher-risk myelodysplastic syndromes (HR-MDS)	Determined by response rates of HR-MDS by disease response criteria	Up to 2.5 years
Secondary	Time to AML transformation		Up to 2.5 years
Secondary	Time to remission for HR-MDS participants		Up to 2.5 years
Secondary	Time to response for HR-MDS participants		Up to 2.5 years
Secondary	Pharmacokinetics-Cmax	Maximum observed concentration in plasma	Up to Day 11
Secondary	Pharmacokinetics - AUC24	Area under the plasma concentration time-curve from time 0 to 24 hours	Up to Day 11
Secondary	Pharmacokinetics - tmax	Time to peak (maximum) plasma concentration	Up to Day 11
Secondary	Pharmacokinetics - t 1/2	terminal half-life	Up to Day 11
Secondary	Pharmacokinetics - CL	Total body clearance of the drug from plasma	Up to Day 11
Secondary	Pharmacokinetics - Vss	Volume of distribution at steady-state	Up to Day 11

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting