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

Sponsor

Celgene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02031419

Collaborator

(none)

174

Enrollment

Locations

Arms

107.4

Anticipated Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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-122 Drug: CC-292 Drug: Rituximab Drug: CC-223 Drug: CC-292 Drug: Rituximab	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

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 :

Dec 18, 2013

Anticipated Primary Completion Date :

Nov 30, 2022

Anticipated Study Completion Date :

Nov 30, 2022

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

Safety [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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].

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sansum Clinic	Santa Barbara	California	United States	93105
2	Stanford Cancer Center	Stanford	California	United States	94305
3	Rocky Mountain Cancer Centers, LLP [Boulder-COBO]	Boulder	Colorado	United States	80303
4	Yale Cancer Center	New Haven	Connecticut	United States	06510
5	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
6	Northwestern University	Chicago	Illinois	United States	60611
7	Illinois Cancer Specialists	Niles	Illinois	United States	60714
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Willamette Valley Cancer Center	Eugene	Oregon	United States	97401-8122
10	West Cancer Center	Germantown	Tennessee	United States	38138
11	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
12	MD Anderson Cancer Center	Houston	Texas	United States	77030-400
13	University of Wisconsin Osteoporosis Clinical Center and Research Program	Madison	Wisconsin	United States	53792
14	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
15	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
16	Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux		France	33076
17	Centre Leon Berard	Lyon		France	69373
18	Gustave Roussy	Villejuif CEDEX		France	94805
19	Istituto Nazionale Dei Tumori	Milano		Italy	20133
20	Istituto Clinico Humanitas	Rozzano (MI)		Italy	20089
21	Azienda Sanitaria Ospedaliera San Giovanni Battista Molinette	Turin		Italy	10126