Clinical Trial: Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study of MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia(CLL)/Small Lymphocytic Lymphoma (SLL)/Prolymphocytic Leukemia (PLL),

Brief Summary: This phase II trial studies how well anti-cluster of differentiation (CD)19 monoclonal antibody MOR00208 and lenalidomide work in treating patients with relapsed, refractory, or previously untreated chronic lymphocytic leukemia, small lymphocytic lymphoma, or prolymphocytic leukemia. Monoclonal antibodies, such as anti-CD19 monoclonal antibody MOR00208, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving anti-CD19 monoclonal antibody MOR00208 and lenalidomide may kill more cancer cells.

Detailed Summary:

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. Sponsor: Ohio State University Comprehensive Cancer Center

Current Primary Outcome: Proportion of patients who achieve a response (i.e. CR, complete response with incomplete recovery [CRi], nPR, or PR), as defined according to the IWCLL 2008 criteria [ Time Frame: up to 6 months ]

Within each cohort, the proportion of patients who achieve an overall response will be estimated by the sum of the number of complete responses, complete responses with incomplete recovery, nodular partial responses, and partial responses divided by the total number of evaluable patients. Ninety percent exact binomial confidence intervals for the true overall response rate will be calculated for those patients included to evaluate the decision criteria.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • ORR [ Time Frame: At 12 months ]
    The ORR with 90% exact binomial confidence intervals will be calculated. The degree of response for evaluable patients will also be summarized. In addition, the number of patients who achieve CR but remain positive for MRD will be documented.
  • PFS [ Time Frame: From the date of registration to date of relapse or death, assessed up to 12 months ]
    PFS will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.
  • Time to next treatment [ Time Frame: From date of registration until date of next treatment or death, censoring those alive who have not started another treatment at last follow-up, assessed up to 12 months ]
    Time to next treatment will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.
  • OS [ Time Frame: From date of registration until date of death or last follow-up, assessed up to 12 months ]
    OS will be summarized with simple descriptive statistics obtained using the Kaplan-Meier method.
  • Results of FISH [ Time Frame: Baseline ]
    Relationships between FISH variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.
  • Results of stimulated karyotype [ Time Frame: Baseline ]
    Relationships between stimulated karyotype variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.
  • Zap-70 methylation [ Time Frame: Baseline ]
    Relationships between Zap-70 variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.
  • IgVH mutational status [ Time Frame: Baseline ]
    Relationships between IgVH variables and ORR or PFS will be explored graphically (e.g. side-by-side boxplots or Kaplan-Meier plots), where estimates with confidence intervals will be presented as the primary method of analysis due to the limited number of patients.
  • Effects of combined therapy with MOR00208 and lenalidomide on CD4+ T cells using flow cytometry during the course of protocol therapy [ Time Frame: Up to 12 months ]
    Patterns will be explored graphically using box plots and/or individual time plots as well as analytically with either repeated measures analysis of variance or Friedman's nonparametric test, recognizing the inherent limitations due to sample size.
  • Effects of combined therapy with MOR00208 and lenalidomide on CD8+ T cells during the course of protocol therapy by flow cytometry [ Time Frame: Up to 12 months ]
    Patterns will be explored graphically using box plots and/or individual time plots as well as analytically with either repeated measures analysis of variance or Friedman's nonparametric test, recognizing the inherent limitations due to sample size.
  • Effects of combined therapy with MOR00208 and lenalidomide on NK cells during the course of protocol therapy by flow cytometry [ Time Frame: Up to 12 months ]
    Patterns will be explored graphically using box plots and/or individual time plots as well as analytically with either repeated measures analysis of variance or Friedman's nonparametric test, recognizing the inherent limitations due to sample size.
  • Changes in IL-21R expression [ Time Frame: Baseline to up to 12 months ]
  • Changes in expression of select genes associated with B-cell activation [ Time Frame: Baseline up to 12 months ]
  • Incidence of adverse events as graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 12 months ]
    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed for each cohort to determine toxicity patterns. The incidence of severe (grade 3+) adverse events or toxicities will be described.
  • Tolerability assessed by the number of patients who require dose modifications and/or dose delays [ Time Frame: Up to 12 months ]


Original Secondary Outcome: Same as current

Information By: Ohio State University Comprehensive Cancer Center

Dates:
Date Received: December 3, 2013
Date Started: December 23, 2013
Date Completion: October 31, 2018
Last Updated: March 1, 2017
Last Verified: March 2017