A clinical study to determine how the drug CC-122 works in the body and to see if it is safe and if it works, when given alone, or in combination with Ibrutinib, or in combination with Obinutuzumab, for people who have Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma.
- Conditions
- Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) based on modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL)MedDRA version: 19.0Level: PTClassification code 10003908Term: B-cell small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: LLTClassification code 10008978Term: Chronic lymphocytic leukemia refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 19.0Level: LLTClassification code 10008977Term: Chronic lymphocytic leukemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10003912Term: B-cell small lymphocytic lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 19.0Level: PTClassification code 10003911Term: B-cell small lymphocytic lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2014-003056-31-ES
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 172
- Subjects >= 18 years age and = 80 years of age at the time of signing the informed
consent form
- Must have a documented diagnosis of CLL/SLL requiring treatment (IWCLL Guidelines
for the Diagnosis and Treatment of CLL [Hallek, 2008]). In addition:
a. Presence of at least one clinically measurable lesion:
i. nodal lesion that measures >= 1.5 cm in longest dimension (LD) and >= 1.0 cm in longest perpendicular dimension (LPD) or
ii. spleen that measures >=14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement or
iii. liver that measures >= 20 cm in LVD with a minimum of 2 cm enlargement or
iv. peripheral blood B lymphocyte count > 5000/uL
- Must meet the criteria for relapsed and/or refractory disease according to the IWCLL guidelines (Hallek, 2008) to >= 1 prior treatment (with the exception of Arm B) and have evidence of disease progression requiring treatment at the time of study entry as follows:
a. For Arms A and C, subjects must have received either prior chemoimmunotherapy or therapy with an approved BTK inhibitor with the following exceptions:
i. Chemoimmunotherapy is not required if subjects have specific comorbidities that preclude the use of standard chemoimmunotherapy meeting at least 1 of the following criteria
1. CIRS >= 6
2. Creatinine Clearance < 70 mL/min
3. Subject is not a candidate for a chemoimmunotherapy in the opinion of investigator
The reason for not being a candidate must be documented in the CRF.
ii. Treatment with an approved BTK inhibitor is not required if subject has contraindications or is not a candidate for such a therapy in the opinion of the investigator
b. For Arm B, subjects with treatment-naïve or R/R CLL must meet the following criteria:
i. Dose Escalation Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have either R/R CLL or treatment naïve (ie, first-line) CLL if the subject:
1. has 17p- and/or TP53 mutation or
2. is unfit for standard chemoimmunotherapy meeting at least 1 of the following co-morbidity criteria:
a. CIRS >= 6;
b. Creatinine Clearance < 70 mL/min;
c. Subject is not a candidate for a chemoimmunotherapy in the opinion of the investigator
ii. Dose Expansion Phase: Subjects must not have received prior treatment with ibrutinib (or any other approved BTK inhibitors) and must have high risk CLL. High risk is defined as:
1) 17p- and/or TP53 mutation positive in treatment naïve CLL or
2) 17p- and/or TP53 mutation positive, and/or complex karyotype, and/or progression <24 months after completion of 1st line chemoimmunotherapy in R/R CLL
c. Subjects with R/R SLL or CLL with bulky disease (at least one lymph node measuring >5.0 cm in diameter) are considered at higher risk for developing TFR and may only be enrolled upon discussion with the sponsor’s medical monitor and agreement to close medical management
- Pregnancy Prevention Risk Management Plan:
a. Females of childbearing potential (FCBP) must undergo pregnancy testing based on
the frequency outlined in the PPRMP and pregnancy results must be negative
b. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods
o For Arm C, subjects must agree to use adequate contraceptive methods for 18 months
c. Males (including those who have had a vasectomy) must practice complete abstinence or use barrier contracepti
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Any condition that confounds the ability to interpret data from the study
- Prior autologous or allogeneic stem cell transplant (SCT)/bone marrow transplant within
12 months of signing the ICD. Subjects who received allogeneic SCT >= 12 months before signing the ICD may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy
-Uncontrolled intercurrent illness including, but not limited to:
a. Ongoing or active infection requiring parenteral antibiotics.
b. Uncontrolled diabetes mellitus.
c. Chronic symptomatic congestive heart failure (Class III or IV of the New York Heart Association Classification for Heart Disease).
d. Active central nervous system involvement as documented by spinal fluid cytology or imaging.
e. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia.
f. Other concurrent severe and/or uncontrolled concomitant medical conditions that could cause unacceptable safety risks or compromise compliance with protocol.
-History of second malignancies with life expectancy of < 2 years or requirement of
therapy that would confound study results. This does not include the following:
a. Basal cell carcinoma of the skin
b. Squamous cell carcinoma of the skin
c. Carcinoma in situ of the cervix
d. Carcinoma in situ of the breast
e. Carcinoma in situ of the bladder
f. Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
- Known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV), or hepatitis B or C virus (HBV, HCV)
-Any peripheral neuropathy >= NCI CTCAE Grade 2
- Use of systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day
-Medicines with high probability to cause QT prolongation or torsades de pointes
Subjects on chronic medications in this category may enroll after discussion with the
medical monitor if changing these medications are not in the best medical interest of the
patient
-History of hypersensitivity to IMiDs®
-Impaired cardiac function or clinically significant cardiac diseases
-Chemotherapy, radiotherapy, investigational anticancer therapy or major surgery within
28 days of Day 1 dosing with the following exceptions:
a. Arm A: A minimum 5-day washout after discontinuation of ibrutinib (or other BTK inhibitors) is required; only those subjects without rapid disease progression during the 5-day washout will be allowed to enroll into Arm A.
b. Arm C: No minimum washout is required after discontinuation of ibrutinib (or other BTK inhibitors)
c. Approved PI3 kinase inhibitors: Subjects may start study treatment within 3 days of discontinuation of approved PI3 kinase inhibitors.
-Persistent diarrhea or malabsorption >= NCI CTCAE Grade 2, despite medical management.
-Active disease transformation (ie, Richter’s Syndrome); subjects with Richter’s Syndrome that has resolved > 2 years from signing the ICD are eligible.
-Known acute or chronic pancreatitis
-Pregnant or lactating females
Arm B only (CC-122 in combination with ibrutinib):
- Prior treatment with a BTK inhibitor
- Presence of transfusion-dependent thrombocytopenia or a history of bleeding disorders or clinic
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method