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

Primary Purpose

Lymphoma, Large B-Cell, Diffuse

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
CC-122
CC-223
Rituximab
CC-122
CC-292
Rituximab
CC-223
CC-292
Rituximab
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Large B-Cell, Diffuse focused on measuring CC-122, CC-223, CC-292, Rituximab, Lymphoma, Diffuse Large B-Cell Lymphoma, Lenalidomide naïve Follicular Lymphoma, Lenalidomide exposed Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 3 months 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].

Sites / Locations

  • Stanford Cancer Center
  • Yale Cancer Center
  • Local Institution - 005
  • Northwestern University
  • Mayo Clinic
  • Local Institution - 001
  • MD Anderson Cancer Center
  • Local Institution - 007
  • Local Institution - 402
  • Local Institution - 400
  • Local Institution - 102
  • Local Institution - 101
  • Local Institution - 100
  • Local Institution - 202
  • Local Institution - 200
  • Local Institution - 201

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

CC-122 + CC-223 +/- rituximab

CC-122 + CC-292 +/- rituximab

CC-292 + CC-223 +/- rituximab

CC-122 + rituximab

Arm Description

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

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

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

CC-122 administered orally once daily in combination with Rituximab.

Outcomes

Primary Outcome Measures

Safety
To determine safety profiles and dose-limiting toxicities of study drug combinations using NCI CTCAE v4.

Secondary Outcome Measures

Efficacy
Tumor response rates using Cheson Revised Response Criteria for Malignant Lymphoma
Pharmacokinetics - CC-223 and CC-292 interaction
Area under the plasma concentration-time curve

Full Information

First Posted
January 7, 2014
Last Updated
October 9, 2023
Sponsor
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT02031419
Brief Title
Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-cell Lymphoma and Follicular Lymphoma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 18, 2013 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Large B-Cell, Diffuse
Keywords
CC-122, CC-223, CC-292, Rituximab, Lymphoma, Diffuse Large B-Cell Lymphoma, Lenalidomide naïve Follicular Lymphoma, Lenalidomide exposed Follicular Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
174 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CC-122 + CC-223 +/- rituximab
Arm Type
Experimental
Arm Description
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
Arm Title
CC-122 + CC-292 +/- rituximab
Arm Type
Experimental
Arm Description
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
Arm Title
CC-292 + CC-223 +/- rituximab
Arm Type
Experimental
Arm Description
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
Arm Title
CC-122 + rituximab
Arm Type
Experimental
Arm Description
CC-122 administered orally once daily in combination with Rituximab.
Intervention Type
Drug
Intervention Name(s)
CC-122
Intervention Description
2mg or 3 mg administered orally once daily
Intervention Type
Drug
Intervention Name(s)
CC-223
Intervention Description
20mg or 30mg administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
375 mg/m2 administered intravenously once every 28 days
Intervention Type
Drug
Intervention Name(s)
CC-122
Intervention Description
2mg or 3mg administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
CC-292
Intervention Description
500 mg twice a day administered orally.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
375 mg/m2 administered intravenously once every 28 days
Intervention Type
Drug
Intervention Name(s)
CC-223
Intervention Description
20mg or 30mg per day administered orally daily.
Intervention Type
Drug
Intervention Name(s)
CC-292
Intervention Description
500 mg twice a day administered orally.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
375 mg/m2 administered intravenously once every 28 days
Primary Outcome Measure Information:
Title
Safety
Description
To determine safety profiles and dose-limiting toxicities of study drug combinations using NCI CTCAE v4.
Time Frame
From the time of informed consent, throughout dosing period and for 28 days after the last dose of study drug.
Secondary Outcome Measure Information:
Title
Efficacy
Description
Tumor response rates using Cheson Revised Response Criteria for Malignant Lymphoma
Time Frame
Every 2-3 months until proof of tumor progression
Title
Pharmacokinetics - CC-223 and CC-292 interaction
Description
Area under the plasma concentration-time curve
Time Frame
Day 1, Day 15

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women, 18 years or older, with histologically or cytologically-confirmed either: Chemo-refractory DLBCL (including transformed low grade lymphoma) 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) 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].
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Cancer Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Local Institution - 005
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Local Institution - 001
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-400
Country
United States
Facility Name
Local Institution - 007
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Local Institution - 402
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Local Institution - 400
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Local Institution - 102
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Local Institution - 101
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Local Institution - 100
City
Villejuif CEDEX
ZIP/Postal Code
94805
Country
France
Facility Name
Local Institution - 202
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Local Institution - 200
City
Rozzano (MI)
ZIP/Postal Code
20089
Country
Italy
Facility Name
Local Institution - 201
City
Turin
ZIP/Postal Code
10126
Country
Italy

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
http://www.BMSStudyConnect.com
Description
BMS Clinical Trial Patient Recruiting

Learn more about this trial

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

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