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

Phase 1TerminatedNCT02848001

Celgene101 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

101

Conditions

Leukemia, Myeloid, Acute Myelodysplastic Syndromes

Interventions

CC-90009DRUG

CC-90009

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (20)

Stanford Cancer Center

Stanford, California, United States

Local Institution - 105

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicity (DLTs)

A participant evaluable for DLT is defined as one that: Has received at least 80% of the total planned Cycle 1 dose (eg, ≥ 4 CC-90009 doses for the Days 1-5 schedule to be completed on or before Day 10, ≥ 6 CC-90009 doses for the Days 1- 7 schedule to be completed on or before Day 10, ≥8 doses by Day 14 for the Days 1-10 schedule, or ≥ 5 doses by Day 14 for the D1-3/D8-10 schedule) of CC-90009 during Cycle 1 without experiencing a DLT, Or; Experienced a DLT after receiving at least one dose (or fraction thereof) of CC-90009 in part A.

Time frame: From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)

Secondary Outcomes

Non-Tolerated Dose (NTD) of CC-90009

The NTD is defined as a dose level at which 2 or more of up to 6 evaluable participants in any dose cohort experience a DLT in Cycle 1 during dose escalation (Part A)

Time frame: From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)

Maximum Tolerated Dose (MTD) of CC-90009

The MTD is defined as the last dose level(s) below the NTD with 0 or 1 out of 6 evaluable participants experiencing a DLT in Cycle 1 during dose escalation (part A).

Time frame: From first dose to at least 28 days and up to 42 days post first dose (Up to 42 days)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Treatment-emergent adverse events (TEAEs) are defined as any AEs that begin on or after the start of study drug through 28 days after the last dose of study drug or serious AEs that are suspected of being related to study drug.

Time frame: From first dose until 28 days post last dose (Up to 25 months)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Local Institution - 102

Chicago, Illinois, United States

Local Institution - 103

Boston, Massachusetts, United States

Local Institution - 101

St Louis, Missouri, United States

Local Institution - 104

Hackensack, New Jersey, United States

Local Institution - 201

Toronto, Ontario, Canada

Local Institution - 505

Lillie Cedex, France

Institut Paoli Calmettes

Marseille, France

Hopital Lyon Sud

Pierre-Bénite, France

...and 10 more locations

Change From Baseline by Laboratory Test - Chemistry Parameters 1

Change from baseline for chemistry laboratory parameters. Baseline = last value before start of treatment