This is a Phase 1b/2 randomized study of Iberdomide (CC-220) added to 3 different combination regimens (polatuzumab vedotin plus rituximab (Cohort A), tafasitamab (Cohort B), rituximab plus gemcitabine and platinum-based chemotherapy (Cohort C)) for participants with relapsed or refractory aggressive B-cell lymphoma (R/R a-BCL). All 3 cohorts will be open for enrollment at study start. Part 1 (dose escalation) will be followed by Part 2 (dose expansion), in which participants will be randomized to one of three cohorts, with CC-220 at the recommended Phase 2 Dose in combination with the Cohorts A, B and C treatment that is compared to their individual standard of care regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Maximum Tolerated Dose (MTD)
Frequency of dose limiting toxicities (DLT) to define MTD of CC- 220 in combination with polatuzumab vedotin plus rituximab or tafasitamab or rituximab plus chemotherapy in subjects with R/R a-BCL.
Time frame: During the First cycle (each cycle is 28 days)
Recommended Phase 2 Dose (RP2D)
Frequency of dose limiting toxicities (DLT) to establish the RP2D of CC- 220 in combination with polatuzumab vedotin plus rituximab or tafasitamab or rituximab plus chemotherapy in subjects with R/R a-BCL.
Time frame: During the First cycle (each cycle is 28 days)
Best Overall Response Rate (ORR)
The proportion of participants with best overall response achieved during the study as either Complete Response or Partial Response before subsequent anti-lymphoma therapy.
Time frame: Up to 7 years
Incidence of Adverse Events (AEs)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant 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 participant'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.
Time frame: From enrollment until at least 28 days after last dose of study treatment
Best ORR- Part 1
The proportion of participants with best overall response achieved during the study as either Complete Response or Partial Response before subsequent anti-lymphoma therapy.
Time frame: Up to 6 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tafasitamab
Gemcitabine
Cisplatin
Dexamethasone
Bendamustine
Lenalidomide
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Avera Cancer Institute
Sioux Falls, South Dakota, United States
Medizinische Universität Graz
Graz, Austria
Universitätsklinikum St. Pölten
Sankt Pölten, Austria
Cliniques Universitaires Saint-Luc
Brussels, Belgium
Hôpital de Jolimont
La Louvière, Belgium
H.-Hartziekenhuis Roeselare-Menen vzw
Roeselare, Belgium
EDOG - Institut Bergonie - PPDS
Bordeaux, France
Hôpital François Mitterand
Dijon, France
...and 17 more locations
Complete Response Rate (CRR)- Part 2
The proportion of participants experiencing Complete Response before receiving any subsequent anti-lymphoma therapy.
Time frame: Up to 7 years
Time to Response (TRR)- Part 2
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to the date of first documented response (≥ PR).
Time frame: Up to 7 years
Duration of Response (DOR)- Part 2
The time from the earliest date of documented response (≥ PR) to the first occurrence of relapse or progression.
Time frame: Up to 7 years
Progression-free Survival (PFS)- Part 2
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to the first occurrence of disease progression or death from any cause.
Time frame: Up to 7 years
Overall Survival (OS)- Part 2
The time from entry to the study (enrollment date for Part 1 and randomization date for Part 2) to death from any cause.
Time frame: Up to 7 years
Pharmacokinetics (PK) - Cmax
Observed maximum CC-220 serum concentration
Time frame: Up to 4 weeks
EORTC QLQ-C30 - Part 2
European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC QLQ-C30) consists of 30 questions incorporated into five functional domains (physical, role, cognitive, emotional, and social), nine symptom scales (fatigue, pain, nausea and vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a single global QoL/global health status score.
Time frame: Up to 7 years
FACT-Lym LymS - Part 2
Functional Assessment of Cancer Therapy-Lymphoma Lymphoma subscale (FACT-Lym LymS) is a 15-item subscale that addresses health-related quality of life symptoms for Non-Hodgkin's lymphoma participants (eg, swelling, night sweats). The FACT instruments use a 5-point intensity type of rating scale (from "not at all" to "very much").
Time frame: Up to 7 years
FACT/GOG-NTX-4 - Part 2
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity 40-item questionnaire (FACT/GOG-NTX-4) is a 4-item peripheral neuropathy subscale used to differentiate between participants with and without treatment-related neurotoxicity. The FACT instruments use a 5-point intensity type of rating scale (from "not at all" to "very much").
Time frame: Up to 7 years
EQ-5D-5L - Part 2
EQ-5D-5L has 2 components: a descriptive system and a visual analogue scale (VAS). The instrument's descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Time frame: Up to 7 years