Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma

January 16, 2024 updated by: Celgene

A Phase 1B, Multi-Center, Open-Label Study of Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma

First study, at multiple clinical centers, exploring the effects of different combinations of compounds (CC-122, CC-223 ,CC-292 and rituximab) to treat Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Study CC-122-DLBCL-001 is a Phase 1b dose escalation and expansion clinical study of CC 122, CC-223 and CC-292 administered orally as doublets with or without rituximab, in participants with relapsed/refractory DLBCL who have failed standard therapy.

In expansion phase, selected combination will be administered to lenalidomide naïve FL participants and lenalidomide exposed FL participants in addition to relapsed/refractory DLBCL participants.

Study Type

Interventional

Enrollment (Actual)

174

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Local Institution - 402
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Local Institution - 400
  • France
      • Bordeaux, France, 33076
        • Local Institution - 102
      • Lyon, France, 69373
        • Local Institution - 101
      • Villejuif CEDEX, France, 94805
        • Local Institution - 100
  • Italy
      • Milano, Italy, 20133
        • Local Institution - 202
      • Rozzano (MI), Italy, 20089
        • Local Institution - 200
      • Turin, Italy, 10126
        • Local Institution - 201
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale Cancer Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Local Institution - 005
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Local Institution - 001
    • Texas
      • Houston, Texas, United States, 77030-400
        • MD Anderson Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Local Institution - 007

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women, 18 years or older, with histologically or cytologically-confirmed either:

    1. Chemo-refractory DLBCL (including transformed low grade lymphoma)
    2. Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory FL participants with no prior exposure to lenalidomide (FL-1 cohort)
    3. Lenalidomide exposed: relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination
  • At least one site of measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  • Participants must have the following laboratory values:
  • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L (with bone marrow involvement with DLBCL)
  • Hemoglobin (Hgb) ≥ 8 g/dL.
  • Potassium within normal limits
  • Asparate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 X ULN if liver tumor is present.
  • Serum bilirubin ≤ 1.5 x ULN.
  • Estimated serum creatinine clearance of ≥ 50 mL/min
  • Participants must have the following laboratory values:

Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if participants received pegfilgrastim).

  • Males enrolled into treatment arms receiving CC-122 must: Agree to abstain from donating sperm while taking IP and for at least 95 days following discontinuation of IP

Exclusion Criteria:

  • Symptomatic central nervous system involvement.
  • Known symptomatic acute or chronic pancreatitis.
  • Persistent diarrhea or malabsorption despite medical management.
  • Peripheral neuropathy ≥ grade 2
  • Impaired cardiac function or clinically significant cardiac diseases
  • Participants with diabetes on active treatment (for participants treated on CC-223 containing arms only)
  • Prior autologous stem cell transplant (ASCT) ≤ 3 months before first dose.
  • Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
  • Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting study drugs, whichever is shorter.
  • Participants who have undergone major surgery ≤ 2 weeks prior to starting study drugs.
  • Women who are pregnant or breast feeding. Adults of reproductive potential not willing to employ two forms of birth control.
  • Participants with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV) infection.
  • Participants with treatment-related myelodysplastic syndrome.
  • History of concurrent second cancers requiring active, ongoing systemic treatment.
  • Prior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK inhibitor (PCI-32765) (CC-292 arms only). [Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed].

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CC-122 + CC-223 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
Drug: CC-122
2mg or 3 mg administered orally once daily
Drug: CC-223
20mg or 30mg administered orally once daily.
Drug: Rituximab
375 mg/m2 administered intravenously once every 28 days
Drug: CC-122
2mg or 3mg administered orally once daily.
Drug: CC-223
20mg or 30mg per day administered orally daily.
Experimental: CC-122 + CC-292 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-292 administered orally twice daily at 500 mg with or without Rituximab administered by IV once every 28 days
Drug: CC-122
2mg or 3 mg administered orally once daily
Drug: Rituximab
375 mg/m2 administered intravenously once every 28 days
Drug: CC-122
2mg or 3mg administered orally once daily.
Drug: CC-292
500 mg twice a day administered orally.
Experimental: CC-292 + CC-223 +/- rituximab
CC-292 administered twice daily at 500 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
Drug: CC-223
20mg or 30mg administered orally once daily.
Drug: Rituximab
375 mg/m2 administered intravenously once every 28 days
Drug: CC-223
20mg or 30mg per day administered orally daily.
Drug: CC-292
500 mg twice a day administered orally.
Experimental: CC-122 + rituximab
CC-122 administered orally once daily in combination with Rituximab.
Drug: CC-122
2mg or 3 mg administered orally once daily
Drug: Rituximab
375 mg/m2 administered intravenously once every 28 days
Drug: CC-122
2mg or 3mg administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: From the time of informed consent, throughout dosing period and for 28 days after the last dose of study drug.
To determine safety profiles and dose-limiting toxicities of study drug combinations using NCI CTCAE v4.
From the time of informed consent, throughout dosing period and for 28 days after the last dose of study drug.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy
Time Frame: Every 2-3 months until proof of tumor progression
Tumor response rates using Cheson Revised Response Criteria for Malignant Lymphoma
Every 2-3 months until proof of tumor progression
Pharmacokinetics - CC-223 and CC-292 interaction
Time Frame: Day 1, Day 15
Area under the plasma concentration-time curve
Day 1, Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2013

Primary Completion (Actual)

December 12, 2023

Study Completion (Actual)

December 12, 2023

Study Registration Dates

First Submitted

January 7, 2014

First Submitted That Met QC Criteria

January 7, 2014

First Posted (Estimated)

January 9, 2014

Study Record Updates

Last Update Posted (Estimated)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC-122-DLBCL-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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