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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01732861
First received: November 14, 2012
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Leukemia Lymphocytic Chronic B-Cell
Drug: CC-292
Drug: Lenalidomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Phase 1B, Open-Label Study to Determine the Safety and Activity of CC-292 in Combination With Lenalidomide in Subjects With Relapsed and /or Refractory Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events


Secondary Outcome Measures:
  • Efficacy [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Response rate on IWCLL (International Workshop for Chronic Lymphocytic Leukemia and lymphoma guidelines.

  • PK-Cmax [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration

  • PK-Tmax [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Time to maximum observed plasma concentration

  • PK-λz [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Terminal phase rate constant, determined by linear regression of the terminal points of the log-linear plasma concentration-time curve. Visual assessment will be used to identify the terminal linear phase of the concentration

  • PK-t1/2 [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Estimate of the terminal elimination half-life in plasma

  • PK-AUC (0-t) [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point

  • PK-AUC0-∞ [ Time Frame: Up to 15 days ] [ Designated as safety issue: No ]
    Area under the plasma concentration time curve from time zero extrapolated to infinity.


Estimated Enrollment: 42
Study Start Date: November 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CC-292 + Lenalidomide Drug: CC-292
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.
Drug: Lenalidomide
Lenalidomde will be given once daily on Days 1-28 of 28-day cycles.

Detailed Description:

This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the recommended Phase 2 dose. The starting dose is CC-292 375 mg twice daily and Lenalidomide 10 mg once daily. After review of the data for dose limiting toxicities (DLTs), the second dose level will be enrolled. Doses for this second cohort are CC-292 500 mg twice daily and lenalidomide 10 mg once daily. Additional doses of lenalidomide in combination with CC-292 may be evaluated to accurately determine the maximum tolerated dose. Once the maximum tolerated dose and/or optimal biologic effect has been ascertained, an expansion cohort of 24 subjects may be enrolled.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

- 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:

    1. Absolute Neutrophil Count (ANC) ≤ 1,000 cells/mm3 (1.0 x 109/L)
    2. Platelet count ≤ 50,000/mm3 (50 x 109/L) unless secondary to bone marrow involvement by recent bone marrow aspiration and bone marrow biopsy
    3. 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
    4. Serum bilirubin > 1.5 x ULN or > 3.0 x ULN in cases of Gilbert's Syndrome and documented liver involvement by lymphoma;
    5. Calculated creatinine clearance using the Cockcroft-Gault formula (Cockcroft,1976)
    6. 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.
  • Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within 28 days of Day 1 dosing.
  • Use of systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day within 3 weeks prior to study drug dosing.
  • Concomitant use of medicines known to cause QT prolongation or torsades de pointes.
  • Chronic use of H2 antagonists or proton pump inhibitors or their use within 7 days of first dose.
  • Gastrointestinal abnormalities including the inability to take oral medication, requiring intravenous alimentation, or prior surgical procedure affecting absorption.
  • Prior treatment with Btk (Bruton's tyrosine kinase) inhibitors.
  • Any live vaccinations within 3 weeks from first dose.
  • History of hypersensitivity to immunomodulatory drugs (IMiDs) (eg, lenalidomide, thalidomide, pomalidomide).
  • Disease transformation (ie, Richter's Syndrome [lymphomas] or prolymphocytic leukemia).
  • Patients with uncontrolled hyper or hypothyroidism.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732861

Contacts
Contact: Markus Kocher, PhD 41 32 729 8794 mkocher@celgene.com
Contact: Associate Director, Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, Alabama
Clearview Cancer Center Recruiting
Huntsville, Alabama, United States, 35805
United States, Indiana
Horizon Oncology Research Recruiting
Lafayette, Indiana, United States, 47905
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
United States, Tennessee
The West Clinic Recruiting
Memphis, Tennessee, United States, 38120
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Austria
Universitätsklinik für Innere Medizin Recruiting
Innsbruck, Austria, 6020
Akh Linz Recruiting
Linz, Austria, 4021
Universitätsklinik der PMU Recruiting
Salzburg, Austria, 5020
AKH Wien Recruiting
Wien, Austria, 1090
Medizinische Abteilung-Zentrum für Onkologie und Hämatologie Recruiting
Wien, Austria, 1100
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Pilar Nava-Parada, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01732861     History of Changes
Other Study ID Numbers: CC-292-CLL-001, 2012-003766-41
Study First Received: November 14, 2012
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Austria: Ethikkommission
Austria: Federal Office for Safety in Health Care

Keywords provided by Celgene Corporation:
Chronic Lymphocytic Leukemia
Small Lymphocytic Leukemia

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 16, 2014