Clinical trial NCT04884035: Study of Safety and Efficacy of Iberdomide (CC-220) and CC-99282 Combined With R-CHOP to Treat Lymphoma
Official title: A Phase 1b, Open Label, Global, Multicenter, Dose Determination, Randomized Dose Expansion Study to Determine the Maximum Tolerated Dose, Assess the Safety and Tolerability, Pharmacokinetics and Preliminary Efficacy of Iberdomide (CC-220) in Combination With R-CHOP-21 and CC-99282 in Combination With R-CHOP-21 for Subjects With Previously Untreated Aggressive B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma, B-Cell
Keywords: Iberdomide
CC-220
CC-99282
Phase 1
B-Cell Lymphoma
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2021-05-12
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b study consisting of 2 parts: a dose escalation (Part 1) of CC-220 or CC-99282 added to the standard R-CHOP-21 regimen for first-line treatment of a-BCL. The dose escalation (Part 1) will consist of 2 parallel arms in combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP-21); CC-220 and R-CHOP-21 or CC-99282 and R-CHOP-21. Part 1 will be followed by a randomized dose expansion (Part 2) with CC-220 and/or CC-99282 at the Recommended Phase 2 Dose (RP2D) in combination with R-CHOP-21. A polatuzumab-R-CHP regimen in combination with CC-220 or CC-99282 will be explored with the addition of a new cohort only after the RP2D for the CC-220 and/or CC-99282 and R-CHOP-21 combination has been defined.


Eligibility criteria: Inclusion Criteria:

* Participants 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. Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated, a-BCL according to 2016 WHO classification.
  3. Participant has International Prognostic Index (IPI) score 0-5 in Part 1 and IPI 2-5 in Part 2. For the CELMoD and polatuzumab-R-CHP cohort, the subject must also have IPI score 0 to 5 in Part 2A and IPI 2 to 5 in Part 2B.
  4. Participants must have measurable disease defined by at least one FDG-avid lesion for FDG-avid subtype and one 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).
  5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  6. Participants must have the following laboratory values:

     1. 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 peg-G-CSF)
     2. Hemoglobin (Hb) ≥ 8 g/dL
     3. 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
     4. Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamate pyruvic transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN). In the case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
     5. Serum total bilirubin ≤ 2.0 mg/dL except in cases of Gilbert's syndrome, then ≤ 5.0 mg/dl. Subjects receiving polatuzumab vedotin must have serum total bilirubin \< 1.5 × ULN (26 μmol/L) (corresponding to mild degree as per National Cancer Institute Organ Dysfunction Working Group \[NCI ODWG\] criteria) except in cases of Gilbert's syndrome, then ≤ 3.0 mg/dl (51 μmol/L).
     6. Estimated serum creatinine clearance (CrCl) of ≥ 50 mL/min using the modification of diet in renal disease (MDRD) formula.
  7. All participants 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 or CC-99282 Pregnancy Prevention Plan for Participants in Clinical trials.
  8. Females of childbearing potential (FCBP) must:

     a. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy.
  9. Male participants must:

     1. Practice true abstinence 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 participant from enrollment:

  1. Any significant medical condition, active infection (including SARS-CoV-2 suspected or confirmed), laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
  2. Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
  3. Any other subtype of lymphoma.
  4. Documented or suspected CNS involvement by lymphoma.
  5. Persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
  6. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
  7. Subjects with a history of progressive multifocal leukoencephalopathy.
  8. Chronic systemic immunosuppressive therapy or corticosteroids
  9. Impaired cardiac function or clinically significant cardiac disease, including any of the following:

     a. Left ventricular ejection fraction (LVEF) \< 45% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO)
  10. Major surgery ≤ 2 weeks prior to starting CC-220 or CC-99282; participant must have recovered from any clinically significant effects of recent surgery.
  11. Any condition causing inability to swallow tablets.
  12. Known seropositivity for or active viral infection with human immunodeficiency virus (HIV)
  13. Known chronic active hepatitis B (hepatitis B virus surface antigen \[HBsAg\] positive and/or hepatitis B core antibody \[anti-HBc\] positive with viral DNA positive) or C (positive serology requiring treatment and/or with evidence of liver damage) infection
  14. History of other malignancy, unless being free of the disease for ≥ 3 years; exceptions to the ≥ 3-year time limit include history of the following:

      1. Localized nonmelanoma skin cancer
      2. Carcinoma in situ of the cervix
      3. Carcinoma in situ of the breast
      4. 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.
  15. Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab or polatuzumab vedotin.
  16. Known hypersensitivity to any component of CHOP/CHP regimen.
  17. Known allergy to thalidomide, pomalidomide, or lenalidomide.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) - Part 1
timeFrame: During the first 2 cycles of treatment (each cycle is 21 days)
measure: Recommended Phase 2 Dose (RP2D) - Part 1
timeFrame: During the first cycle of treatment (each cycle is 21 days)
measure: Safety and tolerability of CC-220 and CC-99282 at RP2D - Part 2
timeFrame: From the first dose of any IP until 28 days after the last dose of IP
measure: Maximum Tolerated Dose (MTD) - Part 2A
timeFrame: During the first cycle of treatment (each cycle is 21 days)
measure: Recommended Phase 2 Dose (RP2D) - Part 2A
timeFrame: During the first cycle of treatment (each cycle is 21 days)
Secondary outcomes:
measure: Best overall response rate (ORR)
timeFrame: Up to 4 years
measure: Complete Metabolic Response Rate (CMRR)
timeFrame: Up to 4 years
measure: Time to Response (TTR)
timeFrame: Up to 4 years
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Pharmacokinetics - Cmax for CC-220
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days)
measure: Pharmacokinetics - Ctrough for CC-220
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
measure: Pharmacokinetics - Tmax for CC-220
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
measure: Pharmacokinetics - Cmax for CC-99282
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
measure: Pharmacokinetics - Ctrough for CC-99282
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
measure: Pharmacokinetics - Tmax for CC-99282
timeFrame: At Cycle 1 Day 7, Cycle 1 Day 15, and Cycle 2 Day 7 (each cycle is 21 days
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS
state: Florida
city: Kansas City
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska - Fred and Pamela Buffet Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Local Institution - 501
state: South Australia
city: Perth
country: Australia
facility: Local Institution - 503
city: Waratah
country: Australia
facility: Local Institution - 502
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko"
city: Athens
country: Greece
facility: Attikon University General Hospital
city: Patras
country: Greece
facility: Local Institution - 703
city: Thessaloniki
country: Greece
facility: Georgios Papanikolaou General Hospital of Thessaloniki
city: Seoul
country: Korea, Republic of
facility: Local Institution - 300
city: Seoul
country: Korea, Republic of
facility: Local Institution - 302
city: Seoul
country: Korea, Republic of
facility: Local Institution - 301
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: MCM Krakow - PRATIA - PPDS
city: Poznan
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Poznan
country: Poland
facility: Local Institution - 0706
city: Poznan
country: Poland
facility: Local Institution - UNK0706
city: Slomniki
country: Poland
facility: SP ZOZ Szpital Uniwersytecki w Krakowie
city: Warsaw
country: Poland
facility: Local Institution - 602
city: Wroclaw
country: Poland
facility: Local Institution - 604
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol ICO Badalona
city: Madrid
country: Spain
facility: Local Institution - 204
city: Málaga
country: Spain
facility: H. Virgen de la Victoria
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca - Complejo Asistencial Universitario de Salamanca
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Local Institution - 403
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: