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A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas

NCT04464798

Description:

This Phase 1/2, multicenter, open-label study to evaluate CC-220 alone, as well as in combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and have at least one measurable lesion according to Lugano 2014 classification. Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2 (Dose Expansion).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Classical Hodgkin Lymphoma
  • Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Marginal Zone Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Dose Finding and Safety Study of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas
  • Official Title: A Phase 1/2, Multicenter, Open-label Study to Assess Safety, Pharmacokinetics, and Preliminary Efficacy of CC-220, Alone and in Combination With an Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: CC-220-NHL-001
  • SECONDARY ID: U1111-1254-1772
  • SECONDARY ID: 2020-000354-10
  • NCT ID: NCT04464798

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
CC-220IberdomideCohort A- Monotherapy in R/R lymphoma subjects
RituximabCohort B- CC-220 and rituximab in R/R B-Cell NHL subjects
ObinutuzumabCohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects

Purpose

This Phase 1/2, multicenter, open-label study to evaluate CC-220 alone, as well as in combination with an anti-CD20 mAb (rituximab or obinutuzumab) in subjects with relapsed or refractory (R/R) lymphoma. Subjects must have received at least 2 prior lines of therapy, and have at least one measurable lesion according to Lugano 2014 classification. Study will consist of two parts: Part 1 (Dose Escalation) which will be followed by Part 2 (Dose Expansion).

Trial Arms

NameTypeDescriptionInterventions
Cohort A- Monotherapy in R/R lymphoma subjectsExperimentalSubjects with Relapsed or Refractory (R/R) lymphoma who have been allocated to Cohort A will receive CC-220 monotherapy (MonoT). Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles.
  • CC-220
Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjectsExperimentalSubjects with R/R B-cell Non Hodgkin Lymphoma (NHL) who have been allocated to Cohort B will receive CC-220 in combination with rituximab. Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle up to PD or maximum 24 cycles. Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC infusion at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2.
  • CC-220
  • Rituximab
Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjectsExperimentalSubjects with R/R FL (Grade 1 to 3a) or MZL who have been allocated to Cohort C will receive CC-220 in combination with obinutuzumab. Oral CC-220 at dose specified by cohort dose level from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles. Obinutuzumab will be administered at 1000 mg at C1D1, D8, and D15, and on D1 of every 28-day cycle from C2 to C6.
  • CC-220
  • Obinutuzumab
Cohort D - Monotherapy in other lymphomas subtype subjectsExperimentalSubjects with other lymphoma subtype who have been allocated to Cohort D will receive CC-220 monotherapy (MonoT). - Oral CC-220 at Recommended Phase 2 dose (RP2D) from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles.
  • CC-220
Cohort E - CC-220 and rituximab in B-cell lymphoma subjectsExperimentalSubjects with aggressive B-cell lymphoma who have been allocated to Cohort E will receive CC-220 in combination with rituximab Oral CC-220 at RP2D from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 24 cycles. Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC infusion at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2.
  • CC-220
  • Rituximab
Cohort F - CC-220 and rituximab in FL and MZL subjectsExperimentalSubjects with follicular lymphoma (FL) (1 to 3a) and marginal zone lymphoma (MZL) who have been allocated to Cohort F Part 2 will receive CC-220 in combination with rituximab. Oral CC-220 at RP2D from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles. Rituximab will be administered at 375 mg/m2 IV at C1D1 and then on D8, D15, and D22 of C1 and then every 28-day cycle at D1 from C2 to C5, either by SC infusion at a dose of 1400 mg or by IV infusion at a dose of 375 mg/m2
  • CC-220
  • Rituximab
Cohort G -CC-220 and obinutuzumab in FL and MZL subjectsExperimentalSubjects with FL (1 to 3a) and MZL who have been allocated to Cohort G will receive CC-220 in combination with obinutuzumab. Oral CC-220 at RP2D from Day 1 to 21 of each 28-day cycle, up to PD or a maximum of 12 cycles. Obinutuzumab will be administered at 1000 mg at C1D1, D8, and D15 and on D1 of every 28-day cycle from C2 to C6.
  • CC-220
  • Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).

          2. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to
             2016 World Health Organization (WHO) classification including:

               1. Cohort A and Cohort D: all subtypes including B-cell, T-cell and Natural killer
                  (NK)-cell Non-Hodgkin lymphoma (NHL), and Classical Hodgkin lymphoma (cHL).

               2. Cohort B: all B-cell NHL.

               3. Cohort E: aggressive B-cell lymphoma

               4. Cohorts C, F and G: FL Grade 1 to 3a and MZL

          3. Relapsed or refractory disease according to the following definitions:

               1. Aggressive B-cell lymphoma: after at least 2 prior lines of therapy including
                  R-CHOP-like regimen OR after 1 prior line of standard therapy and being not
                  eligible for Autologous stem cell transplant (ASCT).

               2. Follicular lymphoma (FL) and Marginal zone lymphoma (MZL): following at least 2
                  prior lines of systemic therapy (being previously exposed to at least 1 anti-CD20
                  mAb and 1 alkylating agent).

               3. Mantle cell lymphoma (MCL): following at least 2 prior lines of therapy including
                  at least 1 immunochemotherapy and 1 bruton tyrosine kinase (BTK) inhibitor.

               4. Peripheral T-cell lymphoma (PTCL): following at least 2 prior lines of therapy OR
                  after 1 prior line of standard therapy and being not eligible for any other
                  approved regimen.

               5. Classical Hodgkin lymphoma (cHL): following at least 2 prior systemic lines of
                  therapy and previously exposed to brentuximab vedotin and anti-PD1.

               6. All other subtypes: following at least 2 prior lines of therapy.

               7. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of
                  the indication).

          4. Must have measurable disease defined by at least 1 fluorodeoxyglucose (FDG)-avid
             lesion for FDG-avid subtype and 1 bi-dimensionally measurable (> 1.5 cm in longest
             diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as
             defined by the Lugano classification. Site of measurable disease cannot be previously
             irradiated.

          5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

          6. Must have the following laboratory values:

               1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L

               2. Hemoglobin (Hb) ≥ 8 g/dL.

               3. Platelets (Plt) ≥ 75 x 109/L or ≥ 50 x 109/L

               4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT)
                  and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤
                  2.5 x ULN.

               5. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert's syndrome, then ≤ 3.0
                  ULN.

               6. Estimated serum creatinine clearance of ≥ 50 mL/min

          7. All subjects must:

               1. Have an understanding that the study drug could have a potential teratogenic
                  risk.

               2. Agree to follow all requirements defined in the Pregnancy Prevention Program for
                  CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.

          8. Females of childbearing potential (FCBP1) must:

             a. Have 2 negative pregnancy tests as verified by the Investigator prior to starting
             study treatment. She must agree to ongoing pregnancy testing during the course of the
             study, and after end of study treatment.

          9. Male subjects must:

               1. Practice true abstinence2 or agree to use a condom during sexual contact with a
                  pregnant female or a female of childbearing potential while participating in the
                  study,

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          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. Life expectancy ≤ 3 months.

          4. Diagnosis of lymphoblastic lymphoma.

          5. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid
             potential life-threatening consequences (eg, due to tumor location).

          6. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F)
             or obinutuzumab (for Cohorts C and G).

          7. Prior therapy with the cereblon-modulating drug CC-99282.

          8. Chronic systemic immunosuppressive therapy or corticosteroids.

          9. Prior ASCT ≤ 3 months prior to starting CC-220 or > 3 months AND with unresolved,
             Grade > 1, treatment-related toxicity.

         10. Prior allogeneic stem cell transplant with either standard or reduced intensity
             conditioning ≤ 6 months prior to starting CC-220 or > 6 months with unresolved, Grade
             > 1, treatment-related toxicity.

         11. Hypersensitivity to the active substance or to murine proteins, or to any of the other
             excipients of rituximab or obinutuzumab.

         12. Known allergy to thalidomide, pomalidomide or lenalidomide.

         13. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.

         14. Major surgery ≤ 2 weeks prior to starting CC-220;

         15. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).

         16. Documented or suspected central nervous system (CNS) involvement of disease.

         17. Subject with clinically significant cardiac disease.

         18. Known seropositivity for or active viral infection with human immunodeficiency virus
             (HIV).

         19. Known chronic active hepatitis B

         20. History of other malignancy, unless the subject has been free of the disease for ≥ 3
             years; exceptions to the ≥ 3-year time limit include history of the following:

               1. Incidental histologic finding of prostate cancer (or prostate cancer that has
                  been treated with curative intent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:During the First cycle (each cycle is 28 days)
Safety Issue:
Description:is defined as the dose that satisfies the escalation with overdose control (EWOC) criterion that the posterior probability to have excessive toxicity is less than 25% and has the highest probability of dose-limiting toxicity (DLT) rate being in the target interval (0.16 to 0.33)

Secondary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From first dose to 28 days after last subject discontinues study treatment
Safety Issue:
Description:An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
Measure:Pharmacokinetics - Cmax
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Maximum plasma concentration
Measure:Pharmacokinetics - Ctrough
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Observed plasma concentration at the end of the dosing interval
Measure:Pharmacokinetics - AUC
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Area under the concentration-time curve
Measure:Pharmacokinetics - tmax
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Time to maximum plasma concentration
Measure:Pharmacokinetics - CL/F
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Apparent total plasma clearance
Measure:Pharmacokinetics - V/F
Time Frame:At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)
Safety Issue:
Description:Apparent total volume of distribution
Measure:Overall Response Rate (ORR)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the proportion of subjects with best overall response as either CR or partial response (PR) before subsequent anti-lymphoma therapy
Measure:Complete Response Rate (CRR)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the proportion of subjects experiencing CR before receiving any subsequent anti-lymphoma therapy
Measure:Time to Response (TTR)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the time from first dose date to the date of first documented response (≥ PR)
Measure:Duration of Response (DOR)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the time from first dose date to the date of first documented response (≥ PR)
Measure:Progression-free Survival (PFS)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the time from first dose date to the first occurrence of disease progression or death from any cause
Measure:Overall Survival (OS)
Time Frame:Approximately 5 years
Safety Issue:
Description:is defined as the time from first dose date to death from any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Relapsed or Refractory Lymphomas
  • Lymphomas
  • CC-220
  • Anti-CD20
  • Monoclonal Antibody
  • Pharmacokinetics
  • Safety

Last Updated

July 9, 2020