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Lymphoma, B-CellPhase 1/2NCT04882163

Study to Evaluate Tolerability of Iberdomide (CC-220) in Combination With Polatuzumab Vedotin Plus Rituximab or Tafasitamab or Rituximab Plus Chemotherapy in B-cell Lymphoma

A Phase 1/2 study testing CC-220, Polatuzumab vedotin and Rituximab in people with Lymphoma, B-Cell, run by Celgene at 27 sites in 8 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
CC-220, Polatuzumab vedotin and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
27 sitesin 8 countries
Study dates
10 Oct 2021to 7 Apr 2029
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must satisfy the following criteria to be enrolled in the study:
  • Participant is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  • Participant has histologically confirmed (per local evaluation) diagnosis of, aggressive B-cell lymphoma (a-BCL) according to 2016 WHO classification among the following subtypes:
  • Diffuse large B-cell lymphoma (DLBCL), Not otherwise specified (NOS) including Germinal center B-cell and Activated B-cell types;
  • High-grade B-cell lymphoma, with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements;
  • Primary mediastinal (thymic) large B-cell lymphoma (PMBCL);
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  • Primary cutaneous DLBCL-leg type;
  • Anaplastic lymphoma kinase positive (ALK+) large B-cell lymphoma;
  • Epstein Barr virus positive (EBV+) DLBCL, NOS;
  • Grade 3b Follicular lymphoma (FL).
  • Participants must have relapsed or refractory disease after at least 2 prior lines of therapy including Rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP)-like regimen OR after one prior line of standard therapy and being not eligible for autologous stem cell transplant (ASCT); participants previously treated with CAR-T therapy can be enrolled.
  • Participant must have measurable disease defined by at least one FDG-avid lesion for FDGavid-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).
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Participant must have the following laboratory values:
  • 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 pegylated granulocyte-colony stimulating factor (peg-G-CSF))
  • Hemoglobin ≥ 8 g/dL
  • Platelets ≥ 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
  • Aspartate aminotransferase / serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase / serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN except in the case of documented liver involvement by lymphoma, where ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
  • Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L) except in cases of Gilbert syndrome, then ≤ 5.0 mg/dL (86 μmol/L)
  • Estimated serum creatinine clearance of ≥ 50 mL/minute using the modification of diet in renal disease formula.
  • All participants must:
  • Have an understanding that the study drug could have a potential teratogenic risk.
  • Agree to follow all requirements defined in the Pregnancy Prevention Program for CC-220 Pregnancy Prevention Plan for Participants in Clinical Trials.
  • A female of childbearing potential (FCBP) must:
  • Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy.
  • Male participants must:
  • Practice true abstinence (which must be reviewed on a monthly basis and source documented) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study.

Who cannot join

  • The presence of any of the following will exclude a participant from enrollment:
  • Participant has 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.
  • In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved
  • Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
  • Participant has any other subtype of lymphoma.
  • Participant has received 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.
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  • Participant has received prior therapy with a Cereblon-modulating drug (eg, lenalidomide, avadomide) ≤ 4 weeks prior to starting CC-220.
  • Participant has persistent diarrhea or malabsorption ≥ Grade 2 (NCI-CTCAE v5.0), despite medical management.
  • Participant has peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0).
  • Participant is on chronic systemic immunosuppressive therapy or corticosteroids.
  • Participant has impaired cardiac function or clinically significant cardiac disease.
  • Participant had major surgery ≤ 2 weeks prior to starting CC-220.
  • Participant has known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
  • Participant has known chronic active hepatitis B
  • Participant has history of other malignancy, unless being free of the disease for ≥ 3 years prior to starting study drug; exceptions to the ≥ 3-year time limit include history of the following:
  • Localized non-melanoma skin cancer
  • Carcinoma in situ of the cervix
  • Carcinoma in situ of the breast
  • 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.
  • Participant has current treatment with strong CYP3A4/5 modulators.
  • Participant has known hypersensitivity to any component of planned combination medications in the regimen.
  • Participant has known allergy to thalidomide, pomalidomide, lenalidomide or avadomide.

Trial locations and contacts

27 sites in 8 countries.

27 sites in 8 countries

France5 sites

  • EDOG - Institut Bergonie - PPDS

    Bordeaux, 33076

  • Hôpital François Mitterand

    Dijon, 21000

  • Centre Hospitalier Lyon Sud

    Lyon, 69373

  • EDOG - Institut Claudius Regaud - PPDS

    Toulouse, 31000

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Spain4 sites

  • Hospital Universitario Germans Trias i Pujol

    Badalona, 8916

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Complejo Asistencial Universitario de Salamanca - H. Clinico

    Salamanca, 37007

  • Hospital Universitario Virgen del Rocio - PPDS

    Seville, 41013

Other trials in Spain

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow Scotland, G12 OXL

  • Royal Liverpool University Hospital

    Liverpool, L7 8XP

  • Nottingham University Hospitals NHS Trust

    Nottingham, Ng5 1PB

  • University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

    Southampton, SO16 6YD

Other trials in United Kingdom

United States3 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

Other trials in United States

Belgium3 sites

  • Cliniques Universitaires Saint-Luc

    Brussels, 1200

  • Hôpital de Jolimont

    La Louvière, 7100

  • H.-Hartziekenhuis Roeselare-Menen vzw

    Roeselare, 8800

Other trials in Belgium

South Korea3 sites

  • Samsung Medical Center

    Seoul, 135-710

  • Asan Medical Center

    Seoul, 138-736

  • Seoul National University Hospital

    Seoul, 3080

Other trials in South Korea

Taiwan3 sites

  • Taipei Veterans General Hospital

    Beitou District, Taipei City, 11217

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Taiwan University Hospital

    Taipei, Zhongzheng Dist., 10002

Other trials in Taiwan

Austria2 sites

  • Medizinische Universität Graz

    Graz, 8036

  • Universitätsklinikum St. Pölten

    Sankt Pölten, 3100

Other trials in Austria

About this study

Official title: A Phase 1B/2 Randomized, Multicenter, Open-Label Study Of Iberdomide (CC-220) In Combination With Polatuzumab Vedotin Plus Rituximab Or Tafasitamab Or Rituximab Plus Chemotherapy For Subjects With Relapsed Or Refractory Aggressive B-Cell Lymphoma

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.

Being tested
CC-220, Polatuzumab vedotin, Rituximab, Tafasitamab, Gemcitabine
Keywords
CC-220, Phase 1B/2, B-Cell Lymphoma
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04882163
Study groupRoleWhat they receive
CC-220 + Polatuzumab vedotin + rituximab- Cohort AExperimentalSubjects with Relapsed or refractory (R/R) Aggressive B-cell lymphoma (a-BCL) will receive CC-220 at a dose specified by cohort dose level in combination with polatuzumab vedotin plus rituximab.
Receives: Drug: CC-220; Drug: Polatuzumab vedotin; Drug: Rituximab
CC-220 + Tafasitamab- Cohort BExperimentalSubjects with R/R a-BCL will receive CC-220 at a dose specified by cohort dose level in combination with tafasitamab.
Receives: Drug: CC-220; Drug: Tafasitamab
CC-220 + Rituximab + Chemo (Cohort C)ExperimentalSubjects with R/R a-BCL will receive CC-220 at a dose specified by cohort dose level in combination with rituximab plus chemotherapy (Gemcitabine, cisplatin, dexamethasone).
Receives: Drug: CC-220; Drug: Rituximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone
CC-220 + Pola + Ritux vs Pola + Benda + Ritux (Cohort D)ExperimentalSubjects will be randomized to receive either CC-220 + Pola (polatuzumab vedotin) + Ritux (rituximab) or polatuzumab vedotin + bendamustine + rituximab in 21-day treatment cycles. CC-220 will be given at the RP2D declared in Part 1 of this study. Polatuzumab vedotin and rituximab will be administered at the same levels as in part 1. Bendamustine will be given to subjects randomized in the control arm at a dose of 90 mg/m2 IV on Days 1 and 2 of each of the first 6 cycles.
Receives: Drug: CC-220; Drug: Polatuzumab vedotin; Drug: Rituximab; Drug: Bendamustine
CC-220 + tafasitamab vs Lenalidomide + Tafasitamab- Cohort EExperimentalSubjects will be randomized to receive either CC-220 + tafasitamab or lenalidomide + tafasitamab in 28-day treatment cycles. CC-220 will be given at the RP2D declared in Part 1 of this study and the tafasitamab will be at the same levels as in Part 1. Lenalidomide will be administered to subjects randomized in the control arm at a dose of 25 mg/day orally, for 21 days out of 28, for up to 12 cycles.
Receives: Drug: CC-220; Drug: Tafasitamab; Drug: Lenalidomide
CC-220 + Rituximab + Chemo vs Rituximab + Chemo (Cohort F)ExperimentalSubjects will be randomized to receive either CC-220 + rituximab + chemotherapy (Gemcitabine, Cisplatin, Dexamethasone) or rituximab + chemotherapy (Gemcitabine, Cisplatin, Dexamethasone) in 21-day treatment cycles. CC-220 will be administered at the RP2D declared in Part 1 of this study and the combination medicines will be at the same levels as in part 1.
Receives: Drug: CC-220; Drug: Rituximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: During the First cycle (each cycle is 28 days)

  2. 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.

    Measured: During the First cycle (each cycle is 28 days)

  3. 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.

    Measured: Up to 7 years

Secondary outcomes (12)

  1. 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.

    Measured: From enrollment until at least 28 days after last dose of study treatment

  2. 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.

    Measured: Up to 6 years

  3. Complete Response Rate (CRR)- Part 2

    The proportion of participants experiencing Complete Response before receiving any subsequent anti-lymphoma therapy.

    Measured: Up to 7 years

  4. 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).

    Measured: Up to 7 years

  5. Duration of Response (DOR)- Part 2

    The time from the earliest date of documented response (≥ PR) to the first occurrence of relapse or progression.

    Measured: Up to 7 years

  6. 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.

    Measured: Up to 7 years

  7. 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.

    Measured: Up to 7 years

  8. Pharmacokinetics (PK) - Cmax

    Observed maximum CC-220 serum concentration

    Measured: Up to 4 weeks

  9. 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.

    Measured: Up to 7 years

  10. 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").

    Measured: Up to 7 years

  11. 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").

    Measured: Up to 7 years

  12. 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.

    Measured: Up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2021
  2. Study start10 Oct 2021 (estimated)
  3. Primary completion8 Apr 2026 (estimated)
  4. Study completion7 Apr 2029 (estimated)

Why it stopped: Business objectives have changed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04882163
Sponsor's protocol ID
CC-220-DLBCL-002
Other IDs
2020-005333-32
Status last verified
Sep 2021
First submitted
6 May 2021
Last updated
5 Oct 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CC-220, Polatuzumab vedotin and Rituximab in people with Lymphoma, B-Cell, run by Celgene at 27 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France, Spain, United Kingdom, United States, Belgium and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: During the First cycle (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04882163.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021.

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