Clinical Trials List
Protocol NumberCC-220-NHL-001
NCT Number(ClinicalTrials.gov Identfier)NCT04464798
Completed
2021-12-15 - 2023-09-01
Phase I/II
Recruiting1
Terminated2
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
-
Sponsor
Celgene
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/12/01
Investigators and Locations
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Ming-Hung Tsai Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
- Chi-Ching Chen Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Wei-Ching Lin Division of Radiology
- Ching Yun Hsieh Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Lymphoma
Objectives
Primary Outcome:
Maximum Tolerated Dose (MTD)
Recommended Phase 2 Dose (RP2D) is defined as the dose that will be selected for dose expansion based on PK/Pd and MTD
Test Drug
Iberdomide (CC-220)
Mabthera (Rituximab)
Gazyva/ Gazyvaro (Obinutuzumab)
Mabthera (Rituximab)
Gazyva/ Gazyvaro (Obinutuzumab)
Active Ingredient
iberdomide
iberdomide
iberdomide
iberdomide
iberdomide
rituximab
rituximab
rituximab
Obinutuzumab
iberdomide
iberdomide
iberdomide
iberdomide
rituximab
rituximab
rituximab
Obinutuzumab
Dosage Form
Capsule
Injections
Injections
Injections
Injections
Dosage
0.6 mg
0.75mg
1mg
1.3mg
1.6mg
100mg/10ml
500mg/50ml
1400mg/11.7ml
1000 mg/40 mL
0.75mg
1mg
1.3mg
1.6mg
100mg/10ml
500mg/50ml
1400mg/11.7ml
1000 mg/40 mL
Endpoints
Primary
Frequency of DLTs to define MTD and establish the RP2D of CC-220 as monotherapy and in combination with rituximab or obinutuzumab
Secondary
Safety and tolerability
PK
Efficacy
Frequency of DLTs to define MTD and establish the RP2D of CC-220 as monotherapy and in combination with rituximab or obinutuzumab
Secondary
Safety and tolerability
PK
Efficacy
Inclution 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. Must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Consents to retrieve formalin-fixed paraffin-embedded (FFPE) archival tumor tissue,
either in tumor blocks or sectioned/mounted specimens, if collected within the last year
and if using in place of biopsy at screening.
5. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to
2016 WHO classification including:
a. Cohort A and Cohort D: all subtypes including B-cell, T-cell and NK-cell NHL, and
cHL.
b. Cohort B: all B-cell NHL.
c. Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell
lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and
PMBCL.
d. Cohorts C, F and G: FL Grade 1 to 3a and MZL including extranodal marginal zone
lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma),
nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma
(SMZL).
6. Relapsed or refractory disease according to the following definitions:
a. Aggressive B-cell lymphoma: after at least 2 prior lines of therapy including
R-CHOP-like regimen.
b. FL and MZL: following at least 2 prior lines of systemic therapy (being previously
exposed to at least 1 anti-CD20 mAb and 1 alkylating agent) and in need for
treatment; local involved field radiotherapy for limited stage disease is not considered
as a previous line. Note: for SMZL, splenectomy is considered as 1 line; for ENMZL,
Helicobacter pylori eradication is not considered as a previous line.
c. MCL: following at least 2 prior lines of therapy including at least 1
immunochemotherapy and 1 BTK inhibitor.
d. 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.
e. cHL: following at least 2 prior systemic lines of therapy and previously exposed to
brentuximab vedotin and anti-PD1.
f. All other subtypes: following at least 2 prior lines of therapy.
g. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of the
indication).
7. Subjects must not be eligible for any other approved treatment for their underlying
lymphoma as assessed by the Investigator.
8. 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 (Cheson, 2014). Site of measurable disease
cannot be previously irradiated.
9. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
10. Must have the following laboratory values:
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109
/L or ≥ 1.0 x 109
/L in case of
documented bone marrow involvement (> 50% or tumor cells), without growth factor
support for 7 days (14 days if pegfilgrastim).
b. Hemoglobin (Hb) ≥ 8 g/dL.
c. Platelets (Plt) ≥ 75 x 109
/L or ≥ 50 x 109
/L in case of documented bone marrow
involvement (> 50% or tumor cells), without transfusion for 7 days.
d. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT)
and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT)
≤ 2.5 x ULN.
e. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert’s syndrome, then
≤ 3.0 ULN.
f. Estimated serum creatinine clearance of ≥ 50 mL/min using the modification of diet
in renal disease formula or directly determined from the 24-hour urine collection
method (see Appendix G).
11. All subjects must:
a. Have an understanding that the study drug could have a potential teratogenic risk.
b. Agree to refrain from donating blood while on study treatment, during dose
interruptions and for at least 28 days following the last dose of study treatment.
c. Agree not to share study medication with another person.
d. Agree to follow all requirements defined in the Pregnancy Prevention Program (see
Appendix C) for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
12. Females must agree to abstain from breastfeeding during study participation and for at
least 28 days after CC-220 discontinuation and according to the approved rituximab or
obinutuzumab product/prescribing information.
13. 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. This applies even if the subject practices true
abstinence2
from heterosexual contact.
b. Either commit to true abstinence2 from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use, and be able to comply
with two forms of contraception: one highly effective, and one additional effective
(barrier) measure of contraception without interruption 28 days prior to starting
investigational product, during the study treatment (including dose interruptions), and
for at least 28 days after the last dose of CC-220, for 12 months after the last dose of
rituximab or 18 months following the last dose of obinutuzumab, whichever is longer.
Contraception requirements are detailed in Appendix C.
14. Male subjects must:
a. Practice true abstinence2
(which must be reviewed on a monthly basis and source
documented) or agree to use a condom (Appendix C) during sexual contact with a
pregnant female or a female of childbearing potential while participating in the study,
during dose interruptions and for at least 90 days after the last dose of CC-220,
rituximab or obinutuzumab, whichever is longer, even if he has undergone a
successful vasectomy.
b. Must agree to refrain from donating sperm while on study treatment, during dose
interruptions and for at least 90 days following last dose of CC-220, rituximab or
obinutuzumab, whichever is longer.
1. Is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
3. Is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Consents to retrieve formalin-fixed paraffin-embedded (FFPE) archival tumor tissue,
either in tumor blocks or sectioned/mounted specimens, if collected within the last year
and if using in place of biopsy at screening.
5. Has histologically confirmed (per local evaluation) diagnosis of lymphoma according to
2016 WHO classification including:
a. Cohort A and Cohort D: all subtypes including B-cell, T-cell and NK-cell NHL, and
cHL.
b. Cohort B: all B-cell NHL.
c. Cohort E: aggressive B-cell lymphoma including DLBCL NOS, high-grade B-cell
lymphoma, with MYC and BCL2 and/or BCL6 rearrangements, Grade 3b FL and
PMBCL.
d. Cohorts C, F and G: FL Grade 1 to 3a and MZL including extranodal marginal zone
lymphoma (ENMZL) of mucosa-associated lymphoid tissue (MALT lymphoma),
nodal marginal zone lymphoma (NMZL) and splenic marginal zone lymphoma
(SMZL).
6. Relapsed or refractory disease according to the following definitions:
a. Aggressive B-cell lymphoma: after at least 2 prior lines of therapy including
R-CHOP-like regimen.
b. FL and MZL: following at least 2 prior lines of systemic therapy (being previously
exposed to at least 1 anti-CD20 mAb and 1 alkylating agent) and in need for
treatment; local involved field radiotherapy for limited stage disease is not considered
as a previous line. Note: for SMZL, splenectomy is considered as 1 line; for ENMZL,
Helicobacter pylori eradication is not considered as a previous line.
c. MCL: following at least 2 prior lines of therapy including at least 1
immunochemotherapy and 1 BTK inhibitor.
d. 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.
e. cHL: following at least 2 prior systemic lines of therapy and previously exposed to
brentuximab vedotin and anti-PD1.
f. All other subtypes: following at least 2 prior lines of therapy.
g. Subjects previously treated with CAR-T therapy can be enrolled (irrespective of the
indication).
7. Subjects must not be eligible for any other approved treatment for their underlying
lymphoma as assessed by the Investigator.
8. 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 (Cheson, 2014). Site of measurable disease
cannot be previously irradiated.
9. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
10. Must have the following laboratory values:
a. Absolute neutrophil count (ANC) ≥ 1.5 x 109
/L or ≥ 1.0 x 109
/L in case of
documented bone marrow involvement (> 50% or tumor cells), without growth factor
support for 7 days (14 days if pegfilgrastim).
b. Hemoglobin (Hb) ≥ 8 g/dL.
c. Platelets (Plt) ≥ 75 x 109
/L or ≥ 50 x 109
/L in case of documented bone marrow
involvement (> 50% or tumor cells), without transfusion for 7 days.
d. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT)
and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT)
≤ 2.5 x ULN.
e. Serum total bilirubin ≤ 1.5 ULN except in cases of Gilbert’s syndrome, then
≤ 3.0 ULN.
f. Estimated serum creatinine clearance of ≥ 50 mL/min using the modification of diet
in renal disease formula or directly determined from the 24-hour urine collection
method (see Appendix G).
11. All subjects must:
a. Have an understanding that the study drug could have a potential teratogenic risk.
b. Agree to refrain from donating blood while on study treatment, during dose
interruptions and for at least 28 days following the last dose of study treatment.
c. Agree not to share study medication with another person.
d. Agree to follow all requirements defined in the Pregnancy Prevention Program (see
Appendix C) for CC-220 Pregnancy Prevention Plan for Subjects in Clinical Trials.
12. Females must agree to abstain from breastfeeding during study participation and for at
least 28 days after CC-220 discontinuation and according to the approved rituximab or
obinutuzumab product/prescribing information.
13. 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. This applies even if the subject practices true
abstinence2
from heterosexual contact.
b. Either commit to true abstinence2 from heterosexual contact (which must be reviewed
on a monthly basis and source documented) or agree to use, and be able to comply
with two forms of contraception: one highly effective, and one additional effective
(barrier) measure of contraception without interruption 28 days prior to starting
investigational product, during the study treatment (including dose interruptions), and
for at least 28 days after the last dose of CC-220, for 12 months after the last dose of
rituximab or 18 months following the last dose of obinutuzumab, whichever is longer.
Contraception requirements are detailed in Appendix C.
14. Male subjects must:
a. Practice true abstinence2
(which must be reviewed on a monthly basis and source
documented) or agree to use a condom (Appendix C) during sexual contact with a
pregnant female or a female of childbearing potential while participating in the study,
during dose interruptions and for at least 90 days after the last dose of CC-220,
rituximab or obinutuzumab, whichever is longer, even if he has undergone a
successful vasectomy.
b. Must agree to refrain from donating sperm while on study treatment, during dose
interruptions and for at least 90 days following last dose of CC-220, rituximab or
obinutuzumab, whichever is longer.
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. Any condition that confounds the ability to interpret data from the study.
4. Life expectancy ≤ 3 months.
5. Diagnosis of lymphoblastic lymphoma
6. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid
potential life-threatening consequences (eg, due to tumor location).
7. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F) or
obinutuzumab (for Cohorts C and G).
8. Prior systemic anti-cancer treatment, CAR-T or any T-cell targeting treatment (approved
or investigational), ≤ 5 half-lives or 4 weeks prior to starting CC-220, whichever is
shorter.
9. Prior therapy with a cereblon-modulating drug (eg, lenalidomide or avadomide) ≤ 4
weeks prior to starting CC-220.
10. Prior therapy with the cereblon-modulating drug CC-99282.
11. Current treatment with a strong CYP3A4/5 modulator (including within 2 weeks prior to
dosing).
12. Chronic systemic immunosuppressive therapy or corticosteroids (eg, prednisone or
equivalent not to exceed 10 mg per day within the last 14 days); stable use of inhaled or
topical corticosteroids is allowed.
13. Prior ASCT ≤ 3 months prior to starting CC-220 or > 3 months AND with unresolved,
Grade > 1, treatment-related toxicity. If > 3 months, treatment-related toxicity must be
resolved or be ≤ Grade 1.
14. 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 including clinically significant graft-versus-host
disease (GVHD); the use of topical steroids for ongoing skin, mucosal or ocular GVHD
is permitted. If > 6 months, treatment-related toxicity must be resolved or be Grade 1.
15. Hypersensitivity to the active substance or to murine proteins, or to any of the other
excipients of rituximab or obinutuzumab.
16. Known allergy to thalidomide, pomalidomide or lenalidomide.
17. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.
18. Major surgery ≤ 2 weeks prior to starting CC-220; subject must have recovered from any
clinically significant effects of recent surgery.
19. Prior radiotherapy within 1 month prior to starting CC-220.
20. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
21. Documented or suspected CNS involvement of disease.
22. Persistent diarrhea or malabsorption ≥ Grade 2 (NCI-CTCAE v5.0), despite medical
management.
23. Gastrointestinal disease that may significantly alter the absorption of CC-220.
24. Subject with clinically significant cardiac disease, including the following:
• Heart failure (New York Heart Association Class III or IV).
• Clinically significant abnormal electrocardiogram (ECG) finding at screening.
• Unstable angina or myocardial infarction ≤ 6 months prior to starting.
• Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation or cardiac
conduction abnormalities not mitigated by a pacemaker.
25. Known seropositivity for or active viral infection with human immunodeficiency virus
(HIV).
26. Known chronic active hepatitis B (Hepatitis B surface antigen [HBs Ag] positive and/or
antibody to hepatitis B core antigen [anti-HBc] positive with viral deoxyribonucleic acid
[DNA] positive) or C (positive serology requiring treatment and/or with evidence of liver
damage) infection.
27. 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:
a. Localized non-melanoma skin cancer.
b. Carcinoma in situ of the cervix.
c. Carcinoma in situ of the breast.
d. Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node
Metastasis [TNM] staging system) or prostate cancer that has been treated with
curative intent.
28. Pregnant or breastfeeding female who intends to become pregnant during participation in
the study
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. Any condition that confounds the ability to interpret data from the study.
4. Life expectancy ≤ 3 months.
5. Diagnosis of lymphoblastic lymphoma
6. Aggressive lymphoma relapse requiring immediate cytoreductive therapy to avoid
potential life-threatening consequences (eg, due to tumor location).
7. Prior Grade 3 or 4 infusion related reaction with rituximab (for Cohorts B, E and F) or
obinutuzumab (for Cohorts C and G).
8. Prior systemic anti-cancer treatment, CAR-T or any T-cell targeting treatment (approved
or investigational), ≤ 5 half-lives or 4 weeks prior to starting CC-220, whichever is
shorter.
9. Prior therapy with a cereblon-modulating drug (eg, lenalidomide or avadomide) ≤ 4
weeks prior to starting CC-220.
10. Prior therapy with the cereblon-modulating drug CC-99282.
11. Current treatment with a strong CYP3A4/5 modulator (including within 2 weeks prior to
dosing).
12. Chronic systemic immunosuppressive therapy or corticosteroids (eg, prednisone or
equivalent not to exceed 10 mg per day within the last 14 days); stable use of inhaled or
topical corticosteroids is allowed.
13. Prior ASCT ≤ 3 months prior to starting CC-220 or > 3 months AND with unresolved,
Grade > 1, treatment-related toxicity. If > 3 months, treatment-related toxicity must be
resolved or be ≤ Grade 1.
14. 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 including clinically significant graft-versus-host
disease (GVHD); the use of topical steroids for ongoing skin, mucosal or ocular GVHD
is permitted. If > 6 months, treatment-related toxicity must be resolved or be Grade 1.
15. Hypersensitivity to the active substance or to murine proteins, or to any of the other
excipients of rituximab or obinutuzumab.
16. Known allergy to thalidomide, pomalidomide or lenalidomide.
17. Inability or unwilling to undergo protocol required thromboembolism prophylaxis.
18. Major surgery ≤ 2 weeks prior to starting CC-220; subject must have recovered from any
clinically significant effects of recent surgery.
19. Prior radiotherapy within 1 month prior to starting CC-220.
20. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
21. Documented or suspected CNS involvement of disease.
22. Persistent diarrhea or malabsorption ≥ Grade 2 (NCI-CTCAE v5.0), despite medical
management.
23. Gastrointestinal disease that may significantly alter the absorption of CC-220.
24. Subject with clinically significant cardiac disease, including the following:
• Heart failure (New York Heart Association Class III or IV).
• Clinically significant abnormal electrocardiogram (ECG) finding at screening.
• Unstable angina or myocardial infarction ≤ 6 months prior to starting.
• Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation or cardiac
conduction abnormalities not mitigated by a pacemaker.
25. Known seropositivity for or active viral infection with human immunodeficiency virus
(HIV).
26. Known chronic active hepatitis B (Hepatitis B surface antigen [HBs Ag] positive and/or
antibody to hepatitis B core antigen [anti-HBc] positive with viral deoxyribonucleic acid
[DNA] positive) or C (positive serology requiring treatment and/or with evidence of liver
damage) infection.
27. 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:
a. Localized non-melanoma skin cancer.
b. Carcinoma in situ of the cervix.
c. Carcinoma in situ of the breast.
d. Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node
Metastasis [TNM] staging system) or prostate cancer that has been treated with
curative intent.
28. Pregnant or breastfeeding female who intends to become pregnant during participation in
the study
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
232 participants
