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

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ClinicalTrials.gov Identifier: NCT02031419
Recruitment Status : Active, not recruiting
First Posted : January 9, 2014
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

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 subjects with relapsed/refractory DLBCL who have failed standard therapy.

In expansion phase, selected combination will be administered to lenalidomide naïve FL subjects and lenalidomide exposed FL subjects in addition to relapsed/refractory DLBCL subjects.


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 : December 15, 2019
Estimated Study Completion Date : November 30, 2020


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




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



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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 subjects 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.
  • Subjects 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
  • Subjects 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 subject 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
  • Subjects with diabetes on active treatment (for subjects 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.
  • Subjects 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.
  • Subjects with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV) infection.
  • Subjects 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].

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02031419


Locations
United States, California
Sansum Clinic
Santa Barbara, California, United States, 93105
Stanford Cancer Center
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Centers, LLP [Boulder-COBO]
Boulder, Colorado, United States, 80303
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
United States, Florida
H. Lee Moffitt Cancer Cencer and Research Institute
Tampa, Florida, United States, 33612
United States, Illinois
Northwestern University, Division of Hematology Oncology, Dept. of Medicine
Chicago, Illinois, United States, 60611
Illinois Cancer Specialists
Niles, Illinois, United States, 60714
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Oregon
Willamette Valley Cancer Center
Eugene, Oregon, United States, 97401-8122
United States, Tennessee
West Cancer Center
Germantown, Tennessee, United States, 38138
Sarah Cannon Cancer Center
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030-400
United States, Wisconsin
University of Wisconsin Osteoporosis Clinical Center and Research Program
Madison, Wisconsin, United States, 53792
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
France
Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest
Bordeaux, France, 33076
Centre Leon Berard
Lyon, France, 69373
Institut Gustave Roussy
Villejuif Cedex, France, 94805
Italy
Istituto Nazionale Dei Tumori
Milano, Italy, 20133
Istituto Clinico Humanitas
Rozzano (MI), Italy, 20089
Azienda Sanitaria Ospedaliera San Giovanni Battista Molinette
Turin, Italy, 10126
Sponsors and Collaborators
Celgene
Investigators
Study Director: Michael Pourdehnad, MD Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02031419     History of Changes
Other Study ID Numbers: CC-122-DLBCL-001
First Posted: January 9, 2014    Key Record Dates
Last Update Posted: September 11, 2018
Last Verified: September 2018

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
Lenalidomide
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors