ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Safety and Efficacy of CC-122 Combined With RCHOP for Newly-diagnosed DLBCL With Poor Risk Factors

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: NCT03283202
Recruitment Status : Recruiting
First Posted : September 14, 2017
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:
This is Phase 1/2 study of CC-122 in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy, for first-line treatment of patients with Diffuse B-Cell Large B-Cell Lymphoma (DLBCL) that has poor risk factors. Approximately 40% of patients diagnosed with DLBCL are not cured with R-CHOP alone and would need additional treatment for DLBCL in the future. The addition of the experimental drug CC-122 with R-CHOP could help in controlling DLBCL in this patient population.

Condition or disease Intervention/treatment Phase
Diffuse B-Cell Lymphoma Drug: CC-122 Drug: Rituximab Drug: Cyclophosphamide 750mg/m2 by IV infusion Drug: Vincristine Drug: Prednisone Phase 1 Phase 2

Detailed Description:

This research study is for patients who have been newly diagnosed with diffuse large B-cell lymphoma DLBCL and are receiving treatment for the first time.

This study will be conducted in two phases. Phase 1 will test the safety of increasing dose levels of CC-122 when given in combination with R-CHOP-21 therapy to identify an appropriate dose and schedule for further evaluation in Phase 2. Phase 2 will evaluate the rate of complete response when adding CC-122 to the R-CHOP-21 regimen in first-line treatment of patients with poor risk DLBCL.

This study is separated into three periods: the Screening period, the Treatment period and the Follow-up period. Before the patient can receive the drug the doctor will perform test to find out whether he/she can participate in the study. This is done during the Screening period. If the patient and the treating physician determine that the patient is eligible to participate in the study, the patient will be registered in the study and receive CC-122 combined with R-CHOP.

In the Treatment period the patient will receive treatment for up to 6 treatment cycles. Each treatment cycle is 21 days long. The full length of the treatment period will be approximately 4 months.

The follow-up period begins when the patient has completed treatment or is discontinued for any reason. During the follow-up period the patient will have fewer exams, test and visits. The first follow-up visit will be 28 days after treatment is completed or discontinued. After that, the follow-up visits will be every 3 months during the first year, then every 6 months until the study is closed.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of CC-122 in Combination With R-CHOP for Previously Untreated Poor-Risk (IPI >=3) Diffuse Large B-Cell Lymphoma and Transformed Lymphomas
Actual Study Start Date : October 4, 2017
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : May 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: CC-122 plus R-CHOP-21
CC-122 by mouth (PO) at varying dose levels (Ph 1) on Days 1 through 5 and Days 8 through 12 plus Rituxan 375 mg/m2 by intravenous (IV) infusion, cyclophosphamide 750mg/m2 by IV infusion, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (max is 2.0 mg) IV and 100 mg PO prednisone/prednisolone on Days 1 through 5 of each 21-day treatment cycles for up to 6 total treatment cycles (approximately 18 weeks or 4 months)
Drug: CC-122
CC-122 by mouth at the assigned dose in Ph 1 starting on Day 1 for 5 consecutive days per week, followed by 2 days without CC-122 administration (5/7) for the first two weeks of a 21-day treatment cycle. If the highest proposed dose level to be explored in Phase 1 is applied, the dosing regimen will be 5/7 days for all 3 weeks of each 21-day treatment cycle.

Drug: Rituximab
Rituxan 375 mg/m2 on Day 1 by intravenous (IV) infusion of a 21-day treatment cycle for up to a total of 6 cycles
Other Name: Rituxan, MabThera

Drug: Cyclophosphamide 750mg/m2 by IV infusion
Cyclophosphamide 750mg/m2 on Day 1 by IV infusion of a 21-day treatment cycle for up to a total of 6 cycles

Drug: Vincristine
Vincristine 1.4 mg/m2 (maximum of 2.0 mg total) on Day 1 by IV bolus on Day 1 of a 21-day treatment cycle for up to a total of 6 cycles
Other Name: Oncovin, Vincasar

Drug: Prednisone
Prednisone 100 mg PO on Days 1 through 5 of each 21-day treatment or 100mg IV on Day 1 is also acceptable for up to a total of 6 cycles
Other Name: Prednisolone




Primary Outcome Measures :
  1. Maximum Tolerated Dose/Maximum Administered Dose (MTD/MAD) (Phase 1) [ Time Frame: Through 6 cycles of treatment (approximately 18 weeks or 4 months) ]
    Frequency of dose-limiting toxicities (DLTs) associated with the addition of CC-122 to R-CHOP-21 therapy

  2. Complete Response Rate (CRR); Percentage of participants experiencing positron emission tomography (PET)-negative complete response (CR) (Phase 2) [ Time Frame: 6 to 8 weeks after completion of treatment ]
    CR is defined as target nodes/nodal masses regress to ≤ 1.5 cm in LDi; no extralymphatic sites of disease; no measurable lesions, no organ enlargement and normal morphology on bone marrow (BM) exam; immunohistochemically (IHC) negative


Secondary Outcome Measures :
  1. Overall Response Rate (ORR); Percentage of participants who achieve a PR or CR according to the Lugano criteria. [ Time Frame: 6 to 8 weeks after completion of treatment ]
    ORR is defined as the rate of the responses (including CR; see definition above for CR and PR; PR is defined as ≥ 50% decrease in sum of perpendicular diameters (SPD) of up to 6 target measurable nodes and extranodal sites. When a lesion is too small to measure on CT, assign 5 mm × 5 mm as the default value; When no longer visible, 0 × 0 mm; for a node > 5 mm × 5 mm, but smaller than normal, use actual measurement for calculation; Absent/normal, regressed, but no increase in non measurable lesions; spleen must have regressed > 50% in length beyond normal and no new lesions.

  2. ORR by Predictive Gene Signature [ Time Frame: 6 to 8 weeks after completion of treatment ]
    ORR by Predictive Gene Signature is defined as the correlation between baseline gene expression signatures and clinical response to study treatment

  3. Progression-free Survival (PFS) [ Time Frame: From enrollment up to 24 months after last subject is enrolled ]
    PFS is defined as the time from enrollment to disease progression or death from any cause

  4. Event-free Survival (EFS) [ Time Frame: At 12 and 24 months after enrollment ]
    EFS is defined as the percentage of participants without event (relapse or progression, unplanned re-treatment of lymphoma after initial immunochemotherapy, or death from any cause)

  5. Overall Survival (OS) [ Time Frame: Up to 24 months after enrollment ]
    OS is defined as the time from enrollment until death from any cause

  6. Adverse Events (AEs) [ Time Frame: From enrollment until at least 28 days after completion of study treatment ]
    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre- existing condition) should be considered an AE.



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:

  1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
  2. Subject has documented, histologically locally confirmed, previously untreated CD20+ DLBCL (NOS) per World Health Organization (WHO) classifications (Swerdlow, 2008).
  3. Subject is considered an appropriate candidate (per Investigator assessment) for induction therapy with 6 cycles of R-CHOP-21 immunochemotherapy.
  4. Subject has a performance status (PS) of 0-2 according to the Eastern Cooperative Oncology Group (ECOG) scale. Subjects with ECOG PS of 3 may be included if decreased PS is secondary to DLBCL only, and not to comorbidities.
  5. Subject has poor-risk disease defined as International Prognostic Index (IPI) score ≥ 3 (high-intermediate or high-risk classification).
  6. Subject has measurable disease on cross-sectional imaging by computed tomography (CT) with at least one (post-biopsy) measurable lesion ≥ 2.0 cm in its longest dimension.
  7. Subject must appropriately be able to complete Screening assessments before beginning treatment for DLBCL, in the judgement of the Investigator.

For subjects with bulky disease, B-symptoms, compressive disease, elevated bilirubin due to lymphoma, rapidly progressing adenopathies, or worsening performance status, pre-phase treatment with up to 100 mg/day prednisone, or equivalent, for a maximum of 10 days is permitted prior to beginning the treatment period, at the discretion of the Investigator. A washout period is not required, however, the Screening positron emission tomography (PET), CT, tumor biopsy (if needed), and bone marrow biopsy (if needed) should be completed before initiating corticosteroids.

8. Subject's central laboratory values must fulfill the following requirements during Screening: Blood product transfusions and hematopoietic growth factors may not be used to meet eligibility criteria. Screening samples should not be collected within 14 days after subject receives a blood product transfusion or growth factors.

  1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 (1.5 x 109/L) unless secondary to extensive bone marrow involvement by lymphoma (ie, ≥ 50%) as demonstrated by unilateral bone marrow core biopsy performed during Screening or within 3 months prior to signing the ICF. In the case of documented extensive bone marrow involvement an ANC ≥ 1,000 cells/mm3 (1.0 x 109/L) is required.
  2. Platelet count ≥ 100,000/mm3 (100 x 109/L) unless secondary to extensive bone marrow involvement by lymphoma (ie, ≥ 50%) as demonstrated by unilateral bone marrow core biopsy performed during Screening or within 3 months prior to signing the ICF. In the case of documented extensive bone marrow involvement, a platelet count of ≥ 75,000/ mm3 (75 x 109/L) is required.
  3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN). In the case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 x ULN.
  4. Serum total bilirubin ≤ 2.0 mg/dL (34 μmol/L). In the case of Gilbert's syndrome, or documented liver or pancreatic involvement by lymphoma, serum total bilirubin must be ≤ 5.0 mg/dL (86 μmol/L).
  5. Calculated creatinine clearance (CrCl) of ≥ 50 mL/min by the Cockcroft-Gault formula.

9. Subject must understand and voluntarily sign an Informed Consent Form (ICF) prior to any study-specific assessments/procedures being conducted.

10. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

11. Sufficient tissue from diagnostic tumor/ lymph node biopsy (from within 2 months prior to ICF signature) must be available for translational research purposes or subject is willing to undergo core needle or incisional/ excisional biopsy during Screening.

12. Females of childbearing potential (FCBP)1 must:

  1. Agree to use two reliable forms of contraception simultaneously or to practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting CC-122; 2) while taking CC-122; 3) during dose interruptions; and 4) for at least 28 days after the last dose of CC-122 as specified in the Pregnancy Prevention and Risk Management Plan (PPRMP)
  2. Have a negative result confirmed for a medically supervised urine (or serum) pregnancy test (with a sensitivity of at least 25 mIU/mL) 10-14 days prior to the first dose of IP. A second pregnancy test performed within 24 hours prior to the first dose of IP must also be confirmed to be negative prior to IP administration.

13. Avoid conceiving for at least 12 months after the last dose of rituximab, or according to the local rituximab Prescribing Information or Summary of Product characteristics (SmPC); at least 28 days after the last dose of any other study drug.

  1. Agree to ongoing pregnancy testing during the course of the study as outlined in the PPRMP.

14. Male subjects must:

  1. Practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) or agree to use a condom during sexual contact with a pregnant female or a FCBP for at least 12 months after the last dose of rituximab.
  2. Agree to not donate semen or sperm for at least 12 months following the last dose of rituximab.

15. All subjects must:

  1. Understand that CC-122 could have a potential teratogenic risk.
  2. Agree to abstain from donating blood while taking IP and for at least 28 days following discontinuation of IP.
  3. Agree not to share IP with another person
  4. Be counseled about pregnancy precautions and risks of fetal exposure and agree to requirements of the Pregnancy Prevention and Risk Management Plan (PPRMP)

16. Subject is able to swallow pills.

Exclusion Criteria:

1. Subject is seropositive for or has active viral infection with hepatitis B virus (HBV):

  1. HBV surface antigen (HBsAg) positive
  2. HBV surface antigen (HBsAg) negative, HBV surface ant ibody (ant i-HBs) posit ive and/or HBV core antibody (ant i-HBc) positive, and detectable viral DNA Subjects who are seropositive because of prior HBV vaccination are eligible (anti- HBs positive, anti-HBc negative, and HBsAg negative).

2. Subject is known to be seropositive for, or have an active infection with, hepatitis C virus (HCV).

3. Subject is known to be seropositive for, or have an active infection with, human immunodeficiency virus (HIV).

4. Subject has any neuropathy > Grade 1. 5. Subject has impaired cardiac function or clinically significant cardiac diseases, including any of the following:

  1. Left ventricular ejection fraction (LVEF) < 45% as determined by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO).
  2. Complete left bundle branch or bifascicular block.
  3. Congenital long QT syndrome
  4. Persistent or clinically meaningful ventricular arrhythmias.
  5. QTcF > 460 msec on Screening electrocardiogram (ECG)
  6. Unstable angina pectoris or myocardial infarction ≤ 3 months prior to starting treatment in the study.
  7. Troponin-T value > 0.4 ng/mL or B-type natriuretic protein (BNP) > 300 pg/mL by central laboratory assessment Subjects with baseline troponin-T > ULN or BNP > 100 pg/mL are eligible but must have a cardiologist evaluation prior to enrollment in the trial for baseline assessment and optimization of cardioprotective therapy.

6. Subject has confirmed central nervous system (CNS) involvement by DLBCL. Subjects at risk for CNS involvement per Investigator assessment must receive prophylaxis. For subjects at risk, or with any neurological symptoms, testing for CNS involvement is required at Screening.

7. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

8. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

9. Subject has any condition that confounds the ability to interpret data from the study.


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): NCT03283202


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

Locations
United States, District of Columbia
George Washington University Recruiting
Washington, District of Columbia, United States, 20037
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Belgium
UZ Gent Recruiting
Gent, Belgium, 9000
University Hospital Gasthuisberg Recruiting
Lueven, Belgium, B-3000
Canada, Alberta
Tom Baker Cancer Center Recruiting
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada, H3T 1E2
Spain
Hospital Germans Trias I Pujol Recruiting
Badalona, Spain, 8916
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 8035
Hospital de San Pedro de Alcantara Not yet recruiting
Caceres, Spain, 10003
Hospital Universitario Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Hospital Clinico Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Hospital Universitario Virgen Del Rocio Recruiting
Sevilla, Spain, 41013
Sponsors and Collaborators
Celgene
Investigators
Study Director: Sabine De Bedout, MD, MPH Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03283202     History of Changes
Other Study ID Numbers: CC-122-DLBCL-002
U1111-1201-1994 ( Registry Identifier: WHO )
2016-003778-42 ( EudraCT Number )
First Posted: September 14, 2017    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Diffuse B-Cell Lymphoma
R-CHOP-21
International Prognostic Index (IPI)

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Prednisone
Vincristine
Prednisolone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Tubulin Modulators