Safety Study of CC-292 and Lenalidomide in Subjects With Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma

NCT01732861 | Completed Phase 1

• 2 other identifiers: CC-292-CLL-0012012-003766-41
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 11

Brief Summary

This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated Dose (MTD). These data will be used to establish a Recommended Phase 2 Dose (RP2D) for the combination of CC-292 and lenalidomide in subjects with Chronic Lymphocytic Leukemia (CLL).

Conditions

Leukemia Lymphocytic Chronic B-Cell

Keywords

Chronic Lymphocytic Leukemia; Small Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Number of participants with adverse events

  Up to 5 years

Secondary Outcomes (7)

• Percentage of Participants Who Have Received Some Form of Response

  Up to 2 years

• PK-Cmax

  Up to 15 days

• PK-Tmax

  Up to 15 days

• PK-λz

  Up to 15 days

• PK-t1/2

  Up to 15 days

Study Arms (1)

CC-292 + Lenalidomide

EXPERIMENTAL

Drug: CC-292; Drug: Lenalidomide

Interventions

CC-292 DRUG

CC-292-will be given twice daily on Days 8-28 of Cycle 1 and on Days 1-28 of the remaining 28-day cycles.

CC-292 + Lenalidomide

Lenalidomide DRUG

Lenalidomde will be given once daily on Days 1-28 of 28-day cycles.

CC-292 + Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects 18 years of age and older at the time of signing the informed consent document (ICD).
• Body weight at least 50 kg.
• Must have a documented diagnosis of CLL/SLL (International Workshop on Chronic Lymphocytic Leukemia IWCLL Guidelines - Hallek 2008) by investigator assessment.
• Have failed at least 1 previous treatments for CLL/SLL, and have relapsed and/or refractory disease following last prior treatment defined as CLL/SLL that does not achieve at least a partial response (PR) to therapy or that progresses within 6 months of treatment.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 or less.
• Life expectancy of at least 3 months from time of signing ICD.
• Females of childbearing potential (FCBP) must have a negative medically supervised pregnancy test prior to starting study therapy and agree to ongoing pregnancy testing during and after end of study therapy; commit to continued abstinence from heterosexual intercourse or agree to use, comply with two effective methods of contraception without interruption, 28 days prior to starting study drug, during study therapy, and for 28 days after discontinuation of study therapy.
• Male subjects must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy, throughout study drug therapy and dose interruption, and for 28 days after end of study therapy; agree to not donate semen or sperm during study drug therapy and for 28 days after end of study drug therapy.
• All subjects must understand that lenalidomide could have a potential teratogenic risk, agree to abstain from donating blood with taking lenalidomide therapy and following discontinuation of study drug therapy; have an echocardiogram (ECG) or multigated acquisition (MUGA) scan of the heart demonstrating left ventricular ejection fraction (LVEF) at least 50% or the institution's lower limit of normal; have recovered from adverse, toxic effects of prior therapies to equal to or less than 1 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 4.03 except for alopecia and peripheral neuropathy.

You may not qualify if:

• \- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Autologous stem cell transplant within 3 months prior to the time of signature on the ICD Informed Consent Document.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring parenteral antibiotics; uncontrolled diabetes mellitus; chronic symptomatic congestive heart failure; unstable angina pectoris, angioplasty, stenting, or myocardial infarctions within 6 months prior to the time of signature on the ICD; clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia. Subjects with controlled atrial fibrillation that is asymptomatic are eligible.
• Pregnant or lactating females.
• Prior history of malignancies, unless the subject has been free of the disease for 5 years or more prior to the time of signature on the ICD. Exceptions to the 5 years or more time limit include history of basal cell carcinoma of the skin; squamous cell carcinoma of the skin; carcinoma in situ of the cervix; carcinoma in situ of the breast; carcinoma in situ of the bladder; incidental histologic finding of prostate cancer (Tumor/Nodes/Metastasis \[TNM\] stage of T1a or T1b).
• Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV).
• Known seropositivity for hepatitis C virus (HCV); hepatitis B virus (HBV).
• Subjects who are at a high risk for a thromboembolic event and are not willing/able to take venous thromboembolic event (VTE) prophylaxis.
• Any of the following laboratory abnormalities:
• Absolute Neutrophil Count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L)
• Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow involvement by recent bone marrow aspiration and bone marrow biopsy
• Serum Aspartate Transaminase/Serum Glutamic-Oxaloacetic Transaminase (AST/SGOT) or Alanine Transaminase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) \> 3.0 x upper limit of normal (ULN) or \> 5.0 x ULN in cases of documented liver involvement
• Serum bilirubin \> 1.5 x ULN or \> 3.0 x ULN in cases of Gilbert's Syndrome and documented liver involvement by lymphoma;
• Calculated creatinine clearance using the Cockcroft-Gault formula (Cockcroft,1976)
• Corrected QT interval (QTc) prolongation (defined as a QTc \> 450 msec for males and \> 470 msec for females \[Fridericia's correction\]) or other clinically significant ECG abnormalities as assessed by the investigator.

Sponsors & Collaborators

• Celgene: lead

Study Sites (11)

Clearview Cancer Institute Oncology Specialties, P.C

Huntsville, Alabama, 35805, United States

Location

Horizon Oncology Center

Lafayette, Indiana, 47905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Universitatsklinik fur Innere Medizin

Innsbruck, Austria

Location

AKh Linz

Linz, 4021, Austria

Location

Universitatsklinik der PMU

Salzburg, 5020, Austria

Location

Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Medizinische Abteilung-Zentrum fur Onkologie und Hamatologie

Vienna, 1100, Austria

Location

MeSH Terms

Conditions

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

spebrutinib; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Liu, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2012
• First Posted: November 26, 2012
• Study Start: December 28, 2012
• Primary Completion: January 23, 2019
• Study Completion: January 23, 2019
• Last Updated: December 20, 2019

Record last verified: 2019-12

Locations

US (6); AU (5)