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

NCT02031419 | Terminated Phase 1

• 1 other identifier: CC-122-DLBCL-001
• Study Type: interventional
• Target: 174
• Locations: 4 countries
• Sites: 16

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Safety

  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 Outcomes (2)

• Efficacy

  Every 2-3 months until proof of tumor progression

• Pharmacokinetics - CC-223 and CC-292 interaction

  Day 1, Day 15

Study Arms (4)

CC-122 + CC-223 +/- rituximab

EXPERIMENTAL

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; Drug: CC-223; Drug: Rituximab

CC-122 + CC-292 +/- rituximab

EXPERIMENTAL

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; Drug: CC-292; Drug: Rituximab

CC-292 + CC-223 +/- rituximab

EXPERIMENTAL

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; Drug: CC-292; Drug: Rituximab

CC-122 + rituximab

EXPERIMENTAL

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

Drug: CC-122; Drug: Rituximab

Interventions

CC-122 DRUG

2mg or 3 mg administered orally once daily

CC-122 + CC-223 +/- rituximab; CC-122 + rituximab

CC-223 DRUG

20mg or 30mg administered orally once daily.

CC-122 + CC-223 +/- rituximab

Rituximab DRUG

375 mg/m2 administered intravenously once every 28 days

CC-122 + CC-223 +/- rituximab; CC-122 + rituximab

CC-292 DRUG

500 mg twice a day administered orally.

CC-122 + CC-292 +/- rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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). \[Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed\].

Sponsors & Collaborators

• Celgene: lead

Study Sites (16)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Local Institution - 005

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Local Institution - 001

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030-400, United States

Location

Local Institution - 007

Madison, Wisconsin, 53792, United States

Location

Local Institution - 402

Edmonton, Alberta, T6G 1Z2, Canada

Location

Local Institution - 400

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 102

Bordeaux, 33076, France

Location

Local Institution - 101

Lyon, 69373, France

Location

Local Institution - 100

Villejuif, 94805, France

Location

Local Institution - 202

Milan, 20133, Italy

Location

Local Institution - 200

Rozzano (MI), 20089, Italy

Location

Local Institution - 201

Turin, 10126, Italy

Location

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione; CC-223; Rituximab; spebrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 9, 2014
• Study Start: December 18, 2013
• Primary Completion: December 12, 2023
• Study Completion: December 12, 2023
• Last Updated: January 18, 2024

Record last verified: 2024-01

Locations

US (8); CA (2); IT (3); FR (3)