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

• ClinicalTrials.gov Identifier: NCT02031419
• Recruitment Status: Active, not recruiting
• First Posted: January 9, 2014
• Last Update Posted: March 14, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

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

Condition or disease	Intervention/treatment	Phase
Lymphoma, Large B-Cell, Diffuse	Drug: CC-122; Drug: CC-223; Drug: Rituximab; Drug: CC-292	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 174 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 18, 2013
• Estimated Primary Completion Date: April 28, 2023
• Estimated Study Completion Date: April 28, 2023

Arms and Interventions

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
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 3mg administered orally once daily.; Drug: CC-292; 500 mg twice a day administered orally.; Drug: Rituximab; 375 mg/m2 administered intravenously once every 28 days
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 per day administered orally daily.; Drug: CC-292; 500 mg twice a day administered orally.; Drug: Rituximab; 375 mg/m2 administered intravenously once every 28 days
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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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].

Contacts and Locations

Sponsors and Collaborators

Celgene

Investigators

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

More Information

Additional Information:

BMS Clinical Trial Information 

BMS Clinical Trial Patient Recruiting 

FDA Safety Alerts and Recalls 

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT02031419
• Other Study ID Numbers: CC-122-DLBCL-001
• First Posted: January 9, 2014
• Last Update Posted: March 14, 2023
• Last Verified: March 2023

Keywords provided by Celgene:

CC-122; CC-223; CC-292; Rituximab; Lymphoma; Diffuse Large B-Cell Lymphoma; Lenalidomide naïve Follicular Lymphoma; Lenalidomide exposed Follicular Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Rituximab; Spebrutinib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action