ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02031419
Recruitment Status : Recruiting
First Posted : January 9, 2014
Last Update Posted : June 7, 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)
Estimated Enrollment : 170 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 : December 15, 2019


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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

  Show 22 Study Locations
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: June 7, 2018
Last Verified: May 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