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Imfinzi NSCLC
JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04464798

Studienbeginn:
November 2020

Letztes Update:
12.05.2021

Wirkstoff:
CC-220, Rituximab, Obinutuzumab

Indikation (Clinical Trials):
Lymphoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Celgene

Collaborator:
-

Studienleiter

Vijaya Kesanakurthy, M.D
Study Director
Celgene/BMS

Kontakt

Associate Director Clinical Trial Disclosure
Kontakt:
Phone: 1-888-260-1599
E-Mail: clinicaltrialdisclosure@celgene.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 20)

Charite - Universitaetsmedizin Berlin Charité - Campus Benjamin Franklin
12203 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
University Hospital Leipzig
4103 Leipzig
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaetsklinikum Muenster
48149 Munster
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps
Universitaetsklinikum Wuerzburg
97080 Wuerzburg
(Bayern)
GermanyRekrutierend» Google-Maps
Mayo Clinic Phoenix
85054 Phoenix
United StatesNoch nicht rekrutierend» Google-Maps
Lake Mary DDU Florida Cancer
32746 Lake Mary
United StatesRekrutierend» Google-Maps
Weill Cornell Medical College - New York Presbyterian Hospital
10065 New York
United StatesRekrutierend» Google-Maps
University of Rochester Cancer Center
14642 Rochester
United StatesRekrutierend» Google-Maps
Sarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-Maps
CHRU de Lille - Hopital Claude Huriez
59037 Lillie Cedex
FranceRekrutierend» Google-Maps
CHU Montpellier - Hôpital Saint Eloi
34295 Montpellier CEDEX 5
FranceRekrutierend» Google-Maps
CHRU - Hopital du Haut Leveque
33604 Pessac
FranceRekrutierend» Google-Maps
I.R.C.C.S. Policlinico San Matteo
27100 Pavia
ItalyRekrutierend» Google-Maps
AOU Integrata Verona - Ospedale Policlinico Giambattista Rossi di Borgo Roma
37134 Verona
ItalyRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

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).

Ein-/Ausschlusskriterien

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.

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. Subjects must not be eligible for any other approved treatment for their underlying

lymphoma as assessed by the Investigator.

5. 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.

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

7. 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

8. 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.

9. 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.

10. 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, active infection (including severe acute

respiratory syndrome coronavirus 2 [SARS-CoV-2) suspected or confirmed, 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.

Studien-Rationale

Primary outcome:

1. Maximum Tolerated Dose (MTD) (Time Frame - During the First cycle (each cycle is 28 days)):
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)

2. Recommended Phase 2 Dose (RR2D) (Time Frame - During the first Cycle (each cycle is 28 days)):
is defined as the dose that will be selected for dose expansion based on PK/Pd and MTD

Secondary outcome:

1. Adverse Events (AEs) (Time Frame - From first dose to 28 days after last subject discontinues study treatment):
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.

2. Pharmacokinetics - Cmax (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Maximum plasma concentration

3. Pharmacokinetics - Ctrough (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Observed plasma concentration at the end of the dosing interval

4. Pharmacokinetics - AUC (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Area under the concentration-time curve

5. Pharmacokinetics - tmax (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Time to maximum plasma concentration

6. Pharmacokinetics - CL/F (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Apparent total plasma clearance

7. Pharmacokinetics - V/F (Time Frame - At Cycle1 Day15 and Cycle2 Day15 (each cycle is 28 days)):
Apparent total volume of distribution

8. Overall Response Rate (ORR) (Time Frame - Approximately 5 years):
is defined as the proportion of subjects with best overall response as either CR or partial response (PR) before subsequent anti-lymphoma therapy

9. Complete Response Rate (CRR) (Time Frame - Approximately 5 years):
is defined as the proportion of subjects experiencing CR before receiving any subsequent anti-lymphoma therapy

10. Time to Response (TTR) (Time Frame - Approximately 5 years):
is defined as the time from enrollment dose date to the date of first documented response (≥ PR)

11. Duration of Response (DOR) (Time Frame - Approximately 5 years):
is defined as the time from first dose date to the date of first documented response (≥ PR)

12. Progression-free Survival (PFS) (Time Frame - Approximately 5 years):
is defined as the time from enrollment date to the first occurrence of disease progression or death from any cause

13. Overall Survival (OS) (Time Frame - Approximately 5 years):
is defined as the time from enrollment date to death from any cause

Studien-Arme

  • Experimental: Cohort A- Monotherapy in R/R lymphoma subjects
    Subjects 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.
  • Experimental: Cohort B- CC-220 and rituximab in R/R B-Cell NHL subjects
    Subjects 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.
  • Experimental: Cohort C - CC-220 and obinutuzumab in R/R FL or MZL subjects
    Subjects 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.
  • Experimental: Cohort D - Monotherapy in other lymphomas subtype subjects
    Subjects 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.
  • Experimental: Cohort E - CC-220 and rituximab in B-cell lymphoma subjects
    Subjects 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.
  • Experimental: Cohort F - CC-220 and rituximab in FL and MZL subjects
    Subjects 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
  • Experimental: Cohort G -CC-220 and obinutuzumab in FL and MZL subjects
    Subjects 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.

Geprüfte Regime

  • CC-220 (Iberdomide):
    Oral
  • Rituximab:
    SC and IV infusion
  • Obinutuzumab:
    IV Infusion

Quelle: ClinicalTrials.gov


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