Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
40

Inclusion Criteria

Inclusion of women and minorities: patients of both genders and all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined; to date, there is no information that suggests that differences in drug metabolism or disease response would be expected in one group compared to another; the small number of patients in a phase II trial precludes any analysis of data to compare patient subgroups based on gender or race/ethnicity
Bilirubin =< 2 times the upper limit of normal, unless related to disease or Gilbert's disease
Patients must provide written informed consent; a signed copy of the consent form will be retained in the patient's chart
...
Inclusion of women and minorities: patients of both genders and all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined; to date, there is no information that suggests that differences in drug metabolism or disease response would be expected in one group compared to another; the small number of patients in a phase II trial precludes any analysis of data to compare patient subgroups based on gender or race/ethnicity
Bilirubin =< 2 times the upper limit of normal, unless related to disease or Gilbert's disease
Patients must provide written informed consent; a signed copy of the consent form will be retained in the patient's chart
Absolute neutrophil count (ANC) >= 1000/mm^3 unless due to CLL involvement of the marrow
Patients capable of reproduction and male patients who have partners capable of reproduction must agree to use an effective contraceptive method during the course of the study and for 2 months following the completion of their last treatment; females of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) pregnancy test result within 3 days of first study dose; female patients who are surgically sterilized or who are > 45 years old and have not experienced menses for > 2 years may have the β-hCG pregnancy test waived
Significant fatigue limiting activity
Unintentional weight loss of 10% or more within 6 months
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal
COHORT 1: previously untreated disease AND refuse or are ineligible for approved chemo- and/or -immunotherapy options for untreated CLL/SLL/PLL
Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
Night sweats > 1 month without evidence of infection
Creatinine =< 2
Patients must be able to receive outpatient treatment and follow-up at the treating institution
Patients must be able to swallow whole capsules
Platelets >= 30 x 10^9/L and absence of active bleeding
Patients with a history of Richter's transformation are eligible if they now have evidence of CLL only, with < 10% large cells in the bone marrow
Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
Fevers >= 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
Patients must have completed all CLL therapies > 4 weeks prior to first study dose; palliative steroids are allowed, but must be at a dose equivalent of =< 20 mg prednisone daily for at least 1 week prior to treatment initiation
Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
COHORT 2: previously received at least one therapy for their disease
Patients must not have secondary cancers that result in a life expectancy of < 2 years or that would confound assessment of toxicity in this study

Exclusion Criteria

Patients who are known to be human immunodeficiency virus (HIV) or hepatitis C positive
Patients with active graft versus host disease or active autoimmune condition related to CLL
Previous treatment with a CD19 antibody; prior lenalidomide is acceptable for patients on cohort 2
...
Patients who are known to be human immunodeficiency virus (HIV) or hepatitis C positive
Patients with active graft versus host disease or active autoimmune condition related to CLL
Previous treatment with a CD19 antibody; prior lenalidomide is acceptable for patients on cohort 2
Patients with active Richter's transformation
Patients with active infections requiring IV antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics or antivirals are acceptable
Patients with a known hypersensitivity to lenalidomide
Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1
Patients with substance abuse or other medical or psychiatric conditions that, in the opinion of the investigator, would confound study interpretation or affect the patient's ability to tolerate or complete the study
Patients who have received alemtuzumab within the previous 6 months
Female subject that is pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception prior to study entry, duration of study participation, and 30 days following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
Patients who have had treatment for CLL within 4 weeks, although palliative steroids are acceptable at doses =< 20 mg prednisone daily
Patients who are known to have hepatitis B infection or who are hepatitis B core antibody or surface antigen positive; patients receiving prophylactic intravenous immunoglobulin (IVIG) may have false positive hepatitis serologies; patients who are on IVIG who have positive hepatitis serologies must have a negative hepatitis B deoxyribonucleic acid (DNA) to be eligible
Patients with congestive heart failure in whom pre-treatment hydration would be prohibitive; New York Heart Association (NYHA) class III/IV congestive heart failure (CHF) is excluded
Patients with a history of prior malignancy other than CLL that requires active systemic therapy that will interfere with interpretation of efficacy or toxicity, or limit survival to 2 years; patients with basal or squamous skin carcinoma, cervical carcinoma in situ on biopsy, localized breast cancer requiring hormonal therapy or localized prostate cancer (Gleason score < 5) are eligible

Summary

Conditions
  • Stage III Chronic Lymphocytic Leukemia
  • Contiguous Stage II Small Lymphocytic Lymphoma
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Prolymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage I Small Lymphocytic Lymphoma
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Small Lymphocytic Lymphoma
  • Stage IV Chronic Lymphocytic Leukemia
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 80 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) at 6 months for patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)/prolymphocytic leukemia (PLL) treated with the combination of MOR00208 plus lenalidomide. II. To determine the ...

PRIMARY OBJECTIVES: I. To determine the overall response rate (ORR) at 6 months for patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)/prolymphocytic leukemia (PLL) treated with the combination of MOR00208 plus lenalidomide. II. To determine the overall response rate (ORR) at 6 months for patients with treatment-naive CLL/SLL/PLL treated with the combination of MOR00208 plus lenalidomide. III.To obtain preliminary data on toxicity profiles and efficacy with the combination of MOR00208 plus lenalidomide in patients with Richter's Transformation IV. To obtain preliminary data on efficacy of MOR00208 in patients with progressive disease on ibrutinib monotherapy SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR) at 12 months for patients with untreated CLL/SLL/PLL or relapsed/refractory disease treated with the combination of MOR00208 plus lenalidomide. II. To determine the complete response (CR) rate, nodular partial response (nPR) rate, partial response (PR) rate, and stable disease (SD) rate for patients with untreated CLL/SLL/PLL or relapsed or refractory disease treated with the combination of MOR00208 plus lenalidomide. III. To summarize the progression free survival (PFS), time to next treatment, and overall survival (OS) for each of two cohorts of patients treated with this regimen. IV. To evaluate toxicity with this regimen, including frequency and severity of toxicities, dose reduction requirements, and adverse events requiring drug discontinuation. V. To perform baseline analysis of patients enrolled on this trial including fluorescence in situ hybridization (FISH), stimulated karyotype, zeta-chain-associated protein kinase 70 (Zap-70) methylation, and immunoglobulin variable region heavy chain (IgVH) mutational status and describe relationships between these biomarkers and ORR or PFS for each of two cohorts with this regimen. VI. To determine the effect of this regimen on total immunoglobulins, CD4+ and CD8+ T cells, natural killer (NK) cells, and interleukin-21 receptor (IL-21R) expression on CLL cells. VII. To determine whether NK cells and T cells are activated in response to MOR00208 alone or in combination with lenalidomide. VIII. To estimate the rate of minimal residual disease (MRD) in patients achieving CR, and whether this correlates with PFS. OUTLINE: Patients receive anti-CD19 monoclonal antibody MOR00208 intravenously (IV) over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1) and lenalidomide orally (PO) daily on days 1-28 (days 9-28 of course 1). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria

Inclusion of women and minorities: patients of both genders and all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined; to date, there is no information that suggests that differences in drug metabolism or disease response would be expected in one group compared to another; the small number of patients in a phase II trial precludes any analysis of data to compare patient subgroups based on gender or race/ethnicity
Bilirubin =< 2 times the upper limit of normal, unless related to disease or Gilbert's disease
Patients must provide written informed consent; a signed copy of the consent form will be retained in the patient's chart
...
Inclusion of women and minorities: patients of both genders and all racial/ethnic groups are eligible for the study if they meet eligibility criteria outlined; to date, there is no information that suggests that differences in drug metabolism or disease response would be expected in one group compared to another; the small number of patients in a phase II trial precludes any analysis of data to compare patient subgroups based on gender or race/ethnicity
Bilirubin =< 2 times the upper limit of normal, unless related to disease or Gilbert's disease
Patients must provide written informed consent; a signed copy of the consent form will be retained in the patient's chart
Absolute neutrophil count (ANC) >= 1000/mm^3 unless due to CLL involvement of the marrow
Patients capable of reproduction and male patients who have partners capable of reproduction must agree to use an effective contraceptive method during the course of the study and for 2 months following the completion of their last treatment; females of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) pregnancy test result within 3 days of first study dose; female patients who are surgically sterilized or who are > 45 years old and have not experienced menses for > 2 years may have the β-hCG pregnancy test waived
Significant fatigue limiting activity
Unintentional weight loss of 10% or more within 6 months
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal
COHORT 1: previously untreated disease AND refuse or are ineligible for approved chemo- and/or -immunotherapy options for untreated CLL/SLL/PLL
Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
Night sweats > 1 month without evidence of infection
Creatinine =< 2
Patients must be able to receive outpatient treatment and follow-up at the treating institution
Patients must be able to swallow whole capsules
Platelets >= 30 x 10^9/L and absence of active bleeding
Patients with a history of Richter's transformation are eligible if they now have evidence of CLL only, with < 10% large cells in the bone marrow
Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
Fevers >= 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
Patients must have completed all CLL therapies > 4 weeks prior to first study dose; palliative steroids are allowed, but must be at a dose equivalent of =< 20 mg prednisone daily for at least 1 week prior to treatment initiation
Massive (>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
COHORT 2: previously received at least one therapy for their disease
Patients must not have secondary cancers that result in a life expectancy of < 2 years or that would confound assessment of toxicity in this study

Exclusion Criteria

Patients who are known to be human immunodeficiency virus (HIV) or hepatitis C positive
Patients with active graft versus host disease or active autoimmune condition related to CLL
Previous treatment with a CD19 antibody; prior lenalidomide is acceptable for patients on cohort 2
...
Patients who are known to be human immunodeficiency virus (HIV) or hepatitis C positive
Patients with active graft versus host disease or active autoimmune condition related to CLL
Previous treatment with a CD19 antibody; prior lenalidomide is acceptable for patients on cohort 2
Patients with active Richter's transformation
Patients with active infections requiring IV antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics or antivirals are acceptable
Patients with a known hypersensitivity to lenalidomide
Failure to recover from toxicity of previous radiotherapy or chemotherapy to grade 1
Patients with substance abuse or other medical or psychiatric conditions that, in the opinion of the investigator, would confound study interpretation or affect the patient's ability to tolerate or complete the study
Patients who have received alemtuzumab within the previous 6 months
Female subject that is pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception prior to study entry, duration of study participation, and 30 days following study completion; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
Patients who have had treatment for CLL within 4 weeks, although palliative steroids are acceptable at doses =< 20 mg prednisone daily
Patients who are known to have hepatitis B infection or who are hepatitis B core antibody or surface antigen positive; patients receiving prophylactic intravenous immunoglobulin (IVIG) may have false positive hepatitis serologies; patients who are on IVIG who have positive hepatitis serologies must have a negative hepatitis B deoxyribonucleic acid (DNA) to be eligible
Patients with congestive heart failure in whom pre-treatment hydration would be prohibitive; New York Heart Association (NYHA) class III/IV congestive heart failure (CHF) is excluded
Patients with a history of prior malignancy other than CLL that requires active systemic therapy that will interfere with interpretation of efficacy or toxicity, or limit survival to 2 years; patients with basal or squamous skin carcinoma, cervical carcinoma in situ on biopsy, localized breast cancer requiring hormonal therapy or localized prostate cancer (Gleason score < 5) are eligible

Locations

Columbus, Ohio, 43210
Columbus, Ohio, 43210

Tracking Information

NCT #
NCT02005289
Collaborators
MorphoSys AG
Investigators
  • Principal Investigator: Jennifer Woyach, MD The Ohio State University Comprehensive Cancer Center
  • Jennifer Woyach, MD The Ohio State University Comprehensive Cancer Center