Clinical Trials /

A Phase 1b Open-label Study to Evaluate the Safety and Efficacy of CC-122 With Obinutuzumab (GA101) in Relapsed/Refractory DLBCL and iNHL.

NCT02417285

Description:

CC-122-NHL-001 study is a multicenter, open-label, phase Ib study with dose escalation and expansion parts. It evaluates the safety, tolerability and clinical pharmacokinetics of CC-122 in combination with obinutuzumab (GA101). The study is also assessing the preliminary efficacy of the combination as well as pharmacodynamic and tumor biomarkers as exploratory objectives. In the dose escalation part, the safety and tolerability of increasing doses of CC-122 administered with a fixed dose of obinutuzumab will be administered to identify the maximum tolerated dose. In the dose expansion part, more patients will be enrolled at a CC-122 dose selected from the escalation part of the study in combination with fixed dose obinutuzumab to further study safety and efficacy.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b Open-label Study to Evaluate the Safety and Efficacy of CC-122 With Obinutuzumab (GA101) in Relapsed/Refractory DLBCL and iNHL.
  • Official Title: A Phase 1b Open-label Study to Evaluate the Safety and Efficacy of CC-122 in Combination With Obinutuzumab (GA101) in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Indolent Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CC-122-NHL-001
  • NCT ID: NCT02417285

Conditions

  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin

Interventions

DrugSynonymsArms
ObinutuzumabGA-101CC-122 in combination with Obinutuzumab
CC-122CC-122 in combination with Obinutuzumab

Purpose

CC-122-NHL-001 study is a multicenter, open-label, phase Ib study with dose escalation and expansion parts. It evaluates the safety, tolerability and clinical pharmacokinetics of CC-122 in combination with obinutuzumab (GA101). The study is also assessing the preliminary efficacy of the combination as well as pharmacodynamic and tumor biomarkers as exploratory objectives. In the dose escalation part, the safety and tolerability of increasing doses of CC-122 administered with a fixed dose of obinutuzumab will be administered to identify the maximum tolerated dose. In the dose expansion part, more patients will be enrolled at a CC-122 dose selected from the escalation part of the study in combination with fixed dose obinutuzumab to further study safety and efficacy.

Detailed Description

      The one or two cohorts during the dose expansion phase (Part B) will enroll subjects with
      relapsed or refractory follicular lymphoma (FL) who were either refractory to or relapsed
      after treatment with a lenalidomide-containing regimen (FL-1 cohort) or never been exposed to
      lenalidomide (FL-2 cohort). The FL-1 and FL-2 cohorts will enroll up to 20 and/or up to 30
      subjects, respectively.
    

Trial Arms

NameTypeDescriptionInterventions
CC-122 in combination with ObinutuzumabExperimentalCC-122 will be administered orally QD starting on Day 1 for 5 consecutive days followed by 2 days off study drug every 7 days (5/7-day schedule) in each 28-day cycle in combination with Obinutuzumab administered as an intravenous (IV) infusion at a dose of 1000 mg on Days 2, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2 through 8.
  • Obinutuzumab
  • CC-122

Eligibility Criteria

        Inclusion Criteria:

          1. Understand and voluntarily sign an informed consent document prior to any study
             related assessments/procedures are conducted.

          2. ≥ 18 years of age or older at the time of signing the informed consent document.

             Entry Criteria Specific for Dose-Escalation Phase (Part A)

          3. Subjects with CD20 positive, histologically or cytologically-confirmed, diffuse large
             B-cell lymphoma (DLBCL)(including transformed low grade lymphoma) who have relapsed or
             refractory disease following at least two prior standard treatment regimens (eg,
             R-CHOP or similar first-lineregimen and at least one second-line salvage regimen)
             and/or autologous stem cell transplant (ASCT) in chemotherapy-sensitive patients, with
             the following ASCT

             EXCEPTIONS:

               -  Subjects in the pre-ASCT setting with poor prognosis, defined as primary
                  refractory disease, that have relapsed within 12 months following first-line
                  treatment; "double-hit" lymphomas with Bcl-2/Myc gene rearrangements or,
                  overexpression or high IPI score (2,3) at relapse.

               -  Subjects refusing ASCT or for whom ASCT is not appropriate based on the
                  Investigator's judgment.

             Entry Criteria Specific for Dose-Expansion Phase (Part B)

          4. Subjects with CD20 positive, histologically confirmed (by WHO 2008 classification
             [Jaffe, 2009]), FL (Grade 1, 2, or 3a) who have relapsed or refractory disease
             following at least one prior standard systemic treatment regimen including systemic
             chemo-, immune-, or chemoimmunotherapy.

             Systemic therapy includes treatments such as rituximab monotherapy, chemotherapy given
             with or without rituximab, radio-immunoconjugates such as 90Y-ibritumomab tiuxetan and
             1311-tositumomab. Systemic therapy does not include, for example, H. pylori
             eradication or antibiotic treatment.

             Lenalidomide naïve

               1. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) following at least
                  one prior standard systemic treatment regimen including systemic chemo-, immune-,
                  or chemoimmunotherapy with no prior exposure to lenalidomide (FL-1 cohort)

                  Lenalidomide exposed

               2. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) previously treated
                  with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either
                  as a single agent or in combination, and experienced outcomes to the lenalidomide
                  treatment as follows:

             Early relapse after lenalidomide treatment: Subjects with relapse within one year of
             last dose of lenalidomide (or a lenalidomide-containing regimen) following initial
             response of Complete Response (CR) to lenalidomide (or a lenalidomide-containing
             regimen) Early progression after lenalidomide treatment: Subjects with Progressive
             Disease (PD) within one year of last dose of lenalidomide (or lenalidomide-containing
             regimen) following initial response of partial response (PR) to lenalidomide (or a
             lenalidomide-containing regimen) Disease refractory to lenalidomide: Subjects with
             best response of stable disease (SD) or PD while on lenalidomide (or
             lenalidomide-containing regimen) without any documented response of PR or better
             during treatment with lenalidomide (or a lenalidomide-containing regimen) Lenalidomide
             or lenalidomide - containing regimen does not need to be the immediate prior regimen
             received by the subject to be eligible for entry.

             Entry Criteria that apply to both Part A and Part B

          5. Subjects with CD20 positive, histologically confirmed (by WHO 2008 classification
             [Jaffe, 2009]), FL (Grade 1, 2, or 3a) who have relapsed or refractory disease
             following at least one prior standard systemic treatment regimen including systemic
             chemo-, immune-, or chemoimmunotherapy.

             Systemic therapy includes treatments such as rituximab monotherapy, chemotherapy given
             with or without rituximab, radio-immunoconjugates such as 90Y-ibritumomab tiuxetan and
             1311-tositumomab. Systemic therapy does not include, for example, H. pylori
             eradication or antibiotic treatment.

             Lenalidomide naïve

               1. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) following at least
                  one prior standard systemic treatment regimen including systemic chemo-, immune-,
                  or chemoimmunotherapy with no prior exposure to lenalidomide (FL 2 cohort). In
                  addition, subjects must have received one prior line of salvage therapy, unless
                  ineligible for autologous transplant.

                  Lenalidomide exposed

               2. Relapsed or refractory follicular lymphoma (Grade 1, 2, or 3a) previously treated
                  with at least two cycles of lenalidomide-containing regimen (FL-1 cohort), either
                  as a single agent or in combination, and experienced outcomes to the lenalidomide
                  treatment as follows:

             Early relapse after lenalidomide treatment: Subjects with relapse within one year of
             last dose of lenalidomide (or a lenalidomide-containing regimen) following initial
             response of Complete Response (CR) to lenalidomide (or a lenalidomide-containing
             regimen) Early progression after lenalidomide treatment: Subjects with Progressive
             Disease (PD) within one year of last dose of lenalidomide (or lenalidomide-containing
             regimen) following initial response of partial response (PR) to lenalidomide (or a
             lenalidomide-containing regimen) Disease refractory to lenalidomide: Subjects with
             best response of stable disease (SD) or PD while on lenalidomide (or
             lenalidomide-containing regimen) without any documented response of PR or better
             during treatment with lenalidomide (or a lenalidomide-containing regimen) Lenalidomide
             or lenalidomide - containing regimen does not need to be the immediate prior regimen
             received by the subject to be eligible for entry.

             Entry Criteria that apply to both Part A and Part B

          6. Bi-dimensionally measurable disease on cross sectional imaging by Computed Tomagraphy
             (CT) or Magnetic resonance imaging (MRI) with at least one lesion > 1.5 cm in the
             transverse diameter, as defined by the International Working Group (IWG) NHL criteria

             Measurable disease cannot be previously irradiated.

          7. ECOG PS (Eastern Cooperative Oncology Group Scale of Performance Status) of 0 to 1.

          8. Subjects must have the following laboratory values at screening:

               -  Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without growth factor support for 7
                  days (14 days if subject received pegfilgrastim).

               -  Hemoglobin (Hgb) ≥ 8 g/dL.

               -  Platelets (plt) ≥ 50 x 109/L without transfusion for 7 days.

               -  Potassium within normal limits or corrected with supplements.

               -  Aspartate aminotransferase/Serum glutamic-oxaloacetic transaminase (AST/SGOT) and
                  Alanine aminotransferase / Serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x
                  Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver tumor is present.

               -  Serum bilirubin ≤1.5 x ULN except in cases of Gilberts Syndrome, then ≤ 2.0 x ULN

               -  Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault
                  equation.

          9. Per the Pregnancy Prevention Risk Management Plan (PPRMP)

               1. Females of childbearing potential (FCBP) must undergo pregnancy testing based on
                  the frequency outlined in PPRMP and pregnancy results must be negative.

               2. Unless practicing complete abstinence from heterosexual intercourse, sexually
                  active FCBP must agree to use adequate contraceptive methods as specified in
                  PPRMP.

                  Complete abstinence is only acceptable in cases where this is the preferred and
                  usual lifestyle of the subject.

                  Periodic abstinence (calendar ovulation, symptothermal, post-ovulation methods)
                  and withdrawal are not acceptable.

               3. Males (including those who have had a vasectomy) must use barrier contraception
                  (condoms) when engaging in sexual activity with FCBP as specified in PPRMP.

               4. Males must agree not to donate semen or sperm for the duration specified in
                  PPRMP.

               5. All subjects must:

                  Understand that the study drugs could have a potential teratogenic risk. Agree to
                  abstain from donating blood while taking study drugs and following
                  discontinuation of investigational product.

                  Agree not to share study drugs with another person.

               6. Other than the subject, FCBP and males able to father a child should not handle
                  the study drugs or touch the capsules, unless gloves are worn.

               7. Be counseled about pregnancy precautions and risks of fetal exposure (refer to
                  PPRMP, Appendix B)

         10. Able to adhere to the study visit schedule and other protocol requirements.

        Exclusion Criteria:

          1. Any significant medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from participating in the study.

          2. Any condition including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study.

          3. Any condition that confounds the ability to interpret data from the study.

          4. Symptomatic central nervous system involvement.

          5. Any history of progressive multifocal leukoencephalopathy (PML).

          6. Known symptomatic acute or chronic pancreatitis.

          7. Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.

          8. Peripheral neuropathy ≥ NCI CTCAE (National Cancer Institute Common Terminology
             Criteria for Adverse Events) Grade 2

          9. Impaired cardiac function or clinically significant cardiac diseases, including any of
             the following:

               -  LVEF (left ventricular ejection fraction) < 45% as determined by MUGA
                  (multi-gated acquisition scan) or ECHO (echocardiogram).

               -  Complete left bundle branch or bifascicular block.

               -  Congenital long QT syndrome.

               -  Persistent or clinically meaningful ventricular arrhythmias.

               -  QTcF > 460 msec on Screening ECG (electrocardiogram) (mean of triplicate
                  recordings as assessed by central read).

               -  Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting
                  study drugs.

               -  Troponin T value > 0.4 ng/mL or BNP > 300 pg/mL

               -  Subjects with baseline troponin T > ULN or BNP > 100 pg/mL are eligible but must
                  have a cardiologist evaluation prior to enrollment in the trial for baseline
                  assessment and optimization of cardioprotective therapy.

         10. Prior ASCT (autologous stem cell transplant) ≤ 3 months before first dose.

         11. Prior allogeneic stem cell transplant with either standard or reduced intensity
             conditioning.

         12. Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives
             or 1 month prior to starting study drugs, whichever is shorter

         13. Prior radiotherapy within 1 month prior to starting study drugs.

         14. A major surgery ≤ 2 weeks prior to starting study drugs. Subjects must have recovered
             from any effects of recent surgery or therapy that might confound the safety
             evaluation of study drug.

         15. Prior treatment with CC-122

         16. History of severe allergic or anaphylactic reactions to humanized monoclonal
             antibodies.

             a. Allergic to any excipients in obinutuzumab.

         17. Known human immunodeficiency virus (HIV) infection.

         18. Known chronic active hepatitis B or C virus (HBV, HCV) infection.

               1. Subjects who are seropositive due to HBV vaccination are eligible.

               2. Subjects who have no active viral infection and are under adequate prophylactics
                  against HBV re-activation are eligible.

         19. Need for current chronic systemic corticosteroid therapy (≥ 10 mg of prednisone per
             day or an equivalent dose of other anti-inflammatory corticosteroids).

             a. Stable use of inhaled corticosteroids is allowed.

         20. Treatment-related myelodysplastic syndrome.

         21. Prior history of secondary malignancies (except for basal cell or squamous cell
             carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject
             has been free of the disease for ≥ 1 year prior to starting study drugs.

         22. Prior immunization with live virus vaccines (within 3 months prior to starting study
             drug) or anticipated immunization with live virus vaccines during the duration of the
             study.

         23. Pregnant or nursing females.

         24. Unwilling or unable to comply with the protocol, in the opinion of the Investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:Approximately 6 years
Safety Issue:
Description:Number of participants with adverse events

Secondary Outcome Measures

Measure:Tumor Response
Time Frame:Approximately 6 years
Safety Issue:
Description:Percentage of subjects with complete response (CR) or partial response (PR) Tumor response will be determined by the Investigator, based on modification of the modified International Working Group (IWG) Response Criteria for Malignant Lymphoma (Cheson,2007) criteria, and summarized using frequency tabulation by dose cohort and tumor type.
Measure:Response Duration
Time Frame:Approximately 6 years
Safety Issue:
Description:Duration from the time when criteria for response (CR or PR) are met to disease relapse/progression using modified IWG evaluation criteria.
Measure:Progression-free Survival (PFS)
Time Frame:Approximately 6 years
Safety Issue:
Description:Number of participants who survive without disease progression/relapse (using modified IWG evaluation criteria) or death as a result of any cause and time from the first dose date to disease progression/relapse or death, whichever occurs first
Measure:Pharmacokinetics - Cmax
Time Frame:up to 8 months
Safety Issue:
Description:Maximum Observed Concentration in plasma
Measure:Pharmacokinetics AUC
Time Frame:Up to 8 months
Safety Issue:
Description:Area under the Concentration-time Curve
Measure:Pharmacokinetics Tmax
Time Frame:Up to 8 months
Safety Issue:
Description:Time to Maximum Concentration
Measure:Pharmacokinetics T1/2
Time Frame:Up to 8 months
Safety Issue:
Description:Terminal half-life (t1/2)
Measure:Pharmacokinetics - CL/F
Time Frame:Up to 8 months
Safety Issue:
Description:Apparent total body clearance
Measure:Pharmacokinetics ‐ Vz/f
Time Frame:Up to 8 months
Safety Issue:
Description:Apparent volume of distribution

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Non-Hodgkin's Lymphoma
  • Diffused Large B-Cell Lymphoma
  • Phase 1B
  • Open-Label
  • Safety and Efficacy
  • CC-122
  • Obinutuzumab
  • GA101
  • Relapsed
  • Refractory

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