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

NCT01744626 | Completed Phase 1

• 2 other identifiers: CC-292-CLL-0022012-003767-21
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 8

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 Rituximab in subjects with CLL.

Conditions

Leukemia Lymphocytic Chronic B-Cell

Keywords

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Number of participants with adverse events

  Up to a year

Secondary Outcomes (7)

• 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

• PK-AUC (0-t)

  Up to 15 days

Study Arms (1)

CC-292 with Rituximab

EXPERIMENTAL

Dose Escalation

Drug: CC-292; Drug: Rituximab

Interventions

CC-292 DRUG

Cohort 1: 375 mg CC-292 will be administered twice a day on Days 1-28 Cohort 2: 500 mg CC-292 will be administered twice a day on Days 1-28

CC-292 with Rituximab

Rituximab DRUG

Cohort 1: Rituximab once per cycle Cohort 2: Rituximab once per cycle

CC-292 with Rituximab

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.
• Understand and voluntarily sign an informed consent document (ICD) prior to any study related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Body weight ≥ 50 kg.
• Must have a documented diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (International Workshop) guidelines for the diagnosis and treatment of CLL (Appendix A), or lymphoma guidelines (Appendix B) for diagnosis and treatment of SLL by investigator assessment.
• Have failed ≥ 1 previous treatments for CLL/SLL, and have relapsed or refractory disease following last prior treatment.
• Refractory is defined as CLL/SLL that does not achieve at least a partial response (PR) to therapy or that progresses within 6 months of treatment. Relapsed CLL/SLL refers to disease that progresses after ≥ 6 months in subjects who had achieved a PR or complete response (CR) to therapy.
• Subjects must have failed, refused, be ineligible, or not otherwise appropriate, per the investigator's judgment, for autologous stem cell transplant (SCT) unless enrollment in this study is anticipated to debulk lesions in preparation for SCT.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤ 2
• Life expectancy of at least 3 months form the time of signing the ICD.
• Females of childbearing potential (FCBP)must have a negative medically supervised pregnancy test prior to starting of study therapy.
• Male subjects must:
• Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug treatment, during any dose interruption and for 28 days after end of study therapy.
• Agree to not donate semen during study drug treatment and for 28 days after end of study drug treatment.
• Ability to swallow oral capsules without difficulty.

You may not qualify if:

• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Autologous stem cell transplant within 3 months of screening date.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring parenteral antibiotics.
• Uncontrolled diabetes mellitus as defined by the investigator.
• Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart. Association Classification for Heart Disease; AppendixG).
• Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months of signing 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 ≥ 3 years of signing the informed consent. Exceptions to the ≥ 3 year time limit include history of the following:
• Basal cell carcinoma of the skin.
• Squamous cell carcinoma of the skin.
• Carcinoma in situ of the cervix.

Sponsors & Collaborators

• Celgene Corporation: lead

Study Sites (8)

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Horizon Oncology Research, Inc

Lafayette, Indiana, 47905, United States

Location

Hackensack UMC

Hackensack, New Jersey, 07601, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Universitätsklinik Ulm

Ulm, Bavaria, 89070, Germany

Location

Städt. Klinikum München-Schwabing

Bayern, 80804, Germany

Location

Universitatsklinikum Wurzburg

Bayern, 907080, Germany

Location

Universitätsklinik Köln

Cologne, 50924, Germany

Location

MeSH Terms

Conditions

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

Interventions

spebrutinib; Rituximab

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kenichi Takeshita, 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: December 5, 2012
• First Posted: December 7, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 19, 2016

Record last verified: 2016-04

Locations

DE (4); US (4)