A Phase 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

NCT02406742 | Completed Phase 1 Results DMC

• 1 other identifier: CC-122-CLL-001
• Study Type: interventional
• Target: 47
• Locations: 5 countries
• Sites: 24

Brief Summary

Safety, pharmacokinetics, and preliminary efficacy of CC-122 alone and in combination with ibrutinib and obinuzutumab. CC-122 has multiple activities, including immune modulation of several immune cell subsets and antiproliferative activity in CLL. CC-122 has also been shown to have a tolerable safety profile with some preliminary signs of efficacy with early human experience.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

CC-122; Pharmacokinetics; Safety; Ibrutinib; Obinutuzumab; GA101; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants and Severity of AEs

  Number and severity of adverse events using the NCI CTCAE criteria (version 4.03), including DLTs

  Approximately 60 Months

• Determination of Non Tolerated Dose (NTD) and Maximum Tolerated Dose (MTD)

  Determination of the NTD and MTD in CC-122 in combination with ibrutinib and CC-122 in combination with obinutuzumab

  52 weeks

Secondary Outcomes (9)

• CC-122 Plasma Concentrations When Administered Alone or in Combination With Ibrutinib or Obinutuzumab

  Approximately 60 Months

• Ibrutinib Plasma Concentrations When Administered in Combination With CC-122

  Approximately 60 Months

• Best Overall Response (BOR)

  Approximately 60 Months

• Minimal Residual Disease Response Rate

  Approximately 60 Months

• Duration of Response

  Approximately 60 Months

Study Arms (3)

CC-122 Single Agent

EXPERIMENTAL

An intrasubject dose escalation design was selected to determine the safety of single agent CC-122 (Arm A) in order to reach an optimal, clinically active dose and to mitigate the risk of early tumor flare reactions, based on earlier experience with lenalidomide monotherapy in CLL.

Drug: CC-122

CC-122 in combination with ibrutinib

EXPERIMENTAL

Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and ibrutinib to determine the NTD, MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee. The RP2D of the combination may be evaluated in ibrutinib-naïve and high-risk CLL patients in the dose expansion phase to continue to evalute safety and efficacy.

Drug: CC-122; Drug: Ibrutinib

CC-122 in combination with obinutuzumab

EXPERIMENTAL

Ascending fixed dose cohorts evaluated in a 3 + 3 dose-finding design will be used to determine the safety and tolerability of the combination of CC-122 and obinutuzumab to determine the , MTD, and Recommended Phase 2 Dose (RP2D). An intrasubject dose escalation cohort may also be evaluated at the discretion of the Safety Review Committee.. The RP2D of the combination may be evaluated in CLL patients who failed a B-cell receptor pathway inhibitor or venetoclax in the dose expansion phase to continue to evalute safety and efficacy.

Drug: CC-122; Drug: Obinutuzumab

Interventions

CC-122 DRUG

CC-122 will be administered daily starting at Cycle 1 Day 1 in 28-day cycles until disease progression, unacceptable toxicity, or discontinuation for any other reason.

CC-122 Single Agent; CC-122 in combination with ibrutinib; CC-122 in combination with obinutuzumab

Ibrutinib DRUG

CC-122 in combination with ibrutinib

Obinutuzumab DRUG

Obinutuzumab will be administered as an intravenous (IV) infusion at a dose of 100 mg on Cycle 1 Day 1 and 900 mg on Cycle 1 Day 2 and 1000 mg on Cycle 1 Days 8 and 15. The dose of obinutuzumab on Days 1 and 2 of Cycle 1 may be adjusted per institutional practice as long as the combined dose equals 1000 mg. Obinutuzumab will be administered at a dose of 1000 mg on Day 1 of Cycles 2 through 6.

CC-122 in combination with obinutuzumab

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed consent form.
• Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
• Able to adhere to the study visit schedule and other protocol requirements.
• Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL guidelines). In addition:
• a. Presence of at least one clinically measurable lesion: i. nodal lesion that measures ≥ 1.5 cm in longest dimension (LD) and ≥ 1.0 cm in longest perpendicular dimension (LPD), or ii. spleen that measures ≥ 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement, or iii. liver that measures ≥ 20 cm in LVD with a minimum of 2 cm enlargement, or iv. peripheral blood B lymphocyte count \> 5000/uL.
• Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to ≥ 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows:
• a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions: i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria;
• \. CIRS ≥ 6; 2. Creatinine Clearance \< 70 mL/min; 3. Subject is not a candidate for a chemoimmunotherapy in the opinion of investigator. ii. Treatment with an approved BTK inhibitor is not required if subject has contraindications or is not a candidate for such a therapy in the opinion of the investigator. b. For Arm B, subjects with treatment-naïve or R/R CLL must meet the following criteria: i. Dose Escalation Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have either R/R CLL or treatment naïve (ie, first-line) CLL if the subject:
• has 17p- and/or TP53 mutation; or
• is unfit for standard chemoimmunotherapy meeting at least 1 of the following co-morbidity criteria: a. CIRS ≥ 6; b. Creatinine Clearance \< 70 mL/min; c. Subject is not a candidate for a chemoimmunotherapy in the opinion of the investigator. The reason for not being a candidate must be documented in CRF. ii. Dose Expansion Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have high risk CLL. High risk is defined as: 1) 17p- and/or TP53 mutation positive in treatment naïve CLL; or 2) 17p- and/or TP53 mutation positive, and/or complex karyotype, and/or progression \< 24 months after completion of 1st line chemoimmunotherapy in R/R CLL c. Subjects with R/R SLL or CLL with bulky disease (at least one lymph node measuring \> 5.0 cm in diameter) are considered at higher risk for developing a TFR and may only be enrolled upon discussion with the sponsor's medical monitor and agreement to close medical management.
• \. Subjects must have the following lab values:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to bone marrow involvement by disease.
• Platelet count ≥ 100,000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x 109/L) if secondary to bone marrow involvement by disease.
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) \< 3.0 x upper limit of normal (ULN) unless due to disease.
• Serum bilirubin \< 1.5 x ULN unless due to Gilbert's syndrome.

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.
• Prior autologous or allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of signing the ICD. Subjects who received allogeneic SCT ≥ 12 months before signing the ICD may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy.
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring parenteral antibiotics.
• Uncontrolled diabetes mellitus.
• i. The glycemic targets for subjects with diabetes should take into consideration age, comorbidities, life expectancy, and functional status of the subjects and follow established guidelines (eg, International Diabetes Federation, the European Diabetes Working Party guidelines, and the American Diabetes Association). For younger (\< 70 years old) or subjects with life expectancy ≥ 10 years, the target glycosylated hemoglobin, type A1C (HbA1c) should be \< 7.0%. The target HbA1c for older (≥ 70 years old) subjects or subjects with life expectancy \< 10 years should be \< 8.0%. Consultation with an endocrinologist is recommended when deciding if diabetes is optimally controlled.
• c. Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease). d. Active central nervous system involvement as documented by spinal fluid cytology or imaging. e. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia. f. Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with protocol.
• History of second malignancies with life expectancy of \< 2 years or requirement of therapy that would confound study results. This does not include the following:
• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (24)

University of California San Diego

La Jolla, California, 92093, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Weill Cornell Medical College Dr. Feldman's Office

New York, New York, 10065, United States

Location

Ohio State University Medical CenterJames Cancer Hospital

Columbus, Ohio, 43210, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

MD Anderson Cancer Center The University of Texas

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98118, United States

Location

University Hospital Innsbruck

Innsbruck, 6020, Austria

Location

University Hospital of Salzburg St Johanns Spital

Salzburg, 5020, Austria

Location

Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Universitat zu Koln

Cologne, 50937, Germany

Location

Universitaetsklinikum EssenInnere Klinik und Poliklinik

Essen, 45147, Germany

Location

University of Schleswig-Holstein

Kiel, 24116, Germany

Location

Universitatsklinikum Würzburg

Würzburg, 97080, Germany

Location

Fondazione Centro San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

Ospedale Niguarda Milano

Milan, 20162, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, 42100, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), 20089, Italy

Location

Hospital Universitario Vall D hebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Daaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione; ibrutinib; obinutuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; 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

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email

Study Officials

• Vijaya Kesanakurthy, MD

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 2, 2015
• Study Start: July 27, 2015
• Primary Completion: July 7, 2020
• Study Completion: July 7, 2020
• Last Updated: September 20, 2021
• Results First Posted: September 20, 2021

Record last verified: 2021-08

Locations

IT (4); US (8); ES (5); AU (3); DE (4)