Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

A Phase 1/2, Open-label, Dose Finding Study to Evaluate CC-122 in Combination With Ibrutinib and Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Protocol: OSU-15056

Full Title

Phase I/II Study To Determine The Safety,Pharmacokinetics, And Efficacy Of Single Agent CC-122 And The Combinations Of CC-122 And Rituximab, CC-122 And Ibrutinib, And CC-122 And Obinutuzumab In Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Purpose

Safety, pharmacokinetics, and preliminary efficacy of CC-122 alone and in combination with

ibrutinib and obinuzutumab.

CC-122 has multiple activities, including immune modulation of several immune cell subsets

and antiproliferative activity in CLL. CC-122 has also been shown to have a tolerable safety

profile with some preliminary signs of efficacy with early human experience.

Study Objective

The primary objectives of this Phase 1/2 Study are to determine the safety of single agent

CC-122 and the safety, tolerability, and RP2D of CC-122 when administered in combination

with ibrutinib and in combination with obinutuzumab to subjects with CLL/SLL. The secondary

objectives are to evaluate the PK profiles of subjects administered CC-122 in combination

with ibrutinib and in combination with obinutuzumab, to determine ibrutinib concentrations

when given alone and in combination with CC-122 and to evaluate the preliminary efficacy of

CC-122 at selected dose levels/regimens.

Are you eligible?

Inclusion Criteria:

Inclusion Criteria:

1. Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed

consent form.

2. Understand and voluntarily sign an informed consent form prior to any study related

assessments/procedures being conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL

guidelines). 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.

5. 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. 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. The

reason for not being a candidate must be documented in CRF. 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 a TFR and may only be enrolled upon discussion with the

sponsor's medical monitor and agreement to close medical management.

6. Subjects must have the following lab values:

1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to

bone marrow involvement by disease.

2. Platelet count ≥ 100,000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x 109/L)

if secondary to bone marrow involvement by disease.

3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x

upper limit of normal (ULN) unless due to disease.

4. Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.

o Serum bilirubin ≤ 1.0 x ULN unless due to Gilbert's syndrome, Treatment Arm B only

(CC-122 in combination with ibrutinib)

5. Calculated creatinine clearance of ≥ 60 ml/min.

6. No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be

enrolled upon correction of electrolyte abnormalities).

7. ECOG PS (Eastern Cooperative Group Performance Status) of 0 or 1. 8. Ability to

swallow oral capsules without difficulty. 9. Pregnancy Prevention Risk Management

Plan:

1. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the

frequency outlined in the Pregnancy Prevention Risk Management Plan (PPRMP) and

pregn

Exclusion Criteria:

Inclusion Criteria:

1. Subjects ≥ 18 years age and ≤ 80 years of age at the time of signing the informed

consent form.

2. Understand and voluntarily sign an informed consent form prior to any study related

assessments/procedures being conducted.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Must have a documented diagnosis of CLL/ SLL requiring treatment (per IWCLL

guidelines). 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.

5. 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. 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. The

reason for not being a candidate must be documented in CRF. 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 a TFR and may only be enrolled upon discussion with the

sponsor's medical monitor and agreement to close medical management.

6. Subjects must have the following lab values:

1. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3 or ≥ 1000 cells/mm3 if secondary to

bone marrow involvement by disease.

2. Platelet count ≥ 100,000 cells/mm3 (100 x 109/L) or ≥ 50,000 cells/mm3 (50 x 109/L)

if secondary to bone marrow involvement by disease.

3. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x

upper limit of normal (ULN) unless due to disease.

4. Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.

o Serum bilirubin ≤ 1.0 x ULN unless due to Gilbert's syndrome, Treatment Arm B only

(CC-122 in combination with ibrutinib)

5. Calculated creatinine clearance of ≥ 60 ml/min.

6. No evidence of TLS per the Cairo-Bishop definition of laboratory TLS (subjects may be

enrolled upon correction of electrolyte abnormalities).

7. ECOG PS (Eastern Cooperative Group Performance Status) of 0 or 1. 8. Ability to

swallow oral capsules without difficulty. 9. Pregnancy Prevention Risk Management

Plan:

1. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the

frequency outlined in the Pregnancy Prevention Risk Management Plan (PPRMP) and

pregn

Leukemia Chronic Lymphocytic Leukemia