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

Lymphoma, Large B-Cell, Diffuse Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02031419
• Other study ID #: CC-122-DLBCL-001
• Status: Terminated
• Phase: Phase 1
• Start date: December 18, 2013
• Est. completion date: December 12, 2023

Study information

• Verified date: January 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 174
• Est. completion date: December 12, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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].

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• CC-122
2mg or 3 mg administered orally once daily
• CC-223
20mg or 30mg administered orally once daily.
• Rituximab
375 mg/m2 administered intravenously once every 28 days
• CC-122
2mg or 3mg administered orally once daily.
• CC-292
500 mg twice a day administered orally.
• Rituximab
375 mg/m2 administered intravenously once every 28 days
• CC-223
20mg or 30mg per day administered orally daily.
• CC-292
500 mg twice a day administered orally.
• Rituximab
375 mg/m2 administered intravenously once every 28 days

Locations

Country	Name	City	State
Canada	Local Institution - 402	Edmonton	Alberta
Canada	Local Institution - 400	Toronto	Ontario
France	Local Institution - 102	Bordeaux
France	Local Institution - 101	Lyon
France	Local Institution - 100	Villejuif CEDEX
Italy	Local Institution - 202	Milano
Italy	Local Institution - 200	Rozzano (MI)
Italy	Local Institution - 201	Turin
United States	Northwestern University	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Local Institution - 007	Madison	Wisconsin
United States	Local Institution - 001	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford Cancer Center	Stanford	California
United States	Local Institution - 005	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy, 

Outcome

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

External Links

•   BMS Clinical Trial Information