Clinical Trial: Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Phase 2 Feasibility Study of Sotrastaurin for Relapsed and Refractory CLL/SLL/PLL/RT

Brief Summary: This phase II trial studies how well sotrastaurin acetate works in treating patients with chronic lymphocytic leukemia, small lymphocytic leukemia, prolymphocytic leukemia, or Richter's transformation that has returned or that does not respond to treatment. Sotrastaurin acetate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the objective clinical response rate of AEB071 (sotrastaurin acetate) treatment in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL)/prolymphocytic leukemia (PLL)/Richter's transformation (RT).

SECONDARY OBJECTIVES:

I. To determine the feasibility and tolerability of long-term administration of a fixed dose of AEB071 in patients with relapsed or refractory CLL/SLL/PLL.

II. To examine select downstream pharmacodynamic effects in this population of patients after receiving AEB071 including assessment of the wingless-type MMTV integration site family (WNT) signaling pathway.

III. To determine the feasibility and tolerability of AEB071 treatment in patients with relapsed or refractory mantle cell lymphoma (MCL) as well as to gain preliminary data regarding efficacy in this patient population.

TERTIARY OBJECTIVES:

I. Determine the proportion of patients with select germline and somatic deoxyribonucleic acid (DNA) alterations, including in the B-cell receptor (BCR) pathway.

II. Determine how mutational and transcriptional status in key genes affects response to this therapy and may have affected response to prior therapies.

OUTLINE:

Patients receive sotrastaurin acetate orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Categories of response for CLL and PLL patients defined according to criteria published by the International Workshop on CLL. Response for SLL/RT patients will be according to revised response criteria for malignant lymphoma. The objective response rate for all evaluable patients in the phase II study will be calculated with an exact 95% binomial confidence interval (assuming that the number of patients who respond is binomially distributed).



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Response duration [ Time Frame: From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Progression free survival (PFS) [ Time Frame: Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Overall survival (OS) [ Time Frame: Time from the first dose of the study drug until death, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Rate of objective clinical response (CR, PR) (optional PLCG2 enriched cohort, if activated) [ Time Frame: Up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Response duration (optional PLCG2 enriched cohort, if activated) [ Time Frame: From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • PFS (optional PLCG2 enriched cohort, if activated) [ Time Frame: Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • OS (optional PLCG2 enriched cohort, if activated) [ Time Frame: Time from the first dose of the study drug until death, assessed up to 3 years ]
    For CLL and PLL patients, defined according to the criteria published by the International Workshop on CLL with the modification outlined by Cheson et al. For SLL/RT patients, responses will be according to revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Rate of objective clinical response (CR, PR) (MCL cohort) [ Time Frame: Up to 3 years ]
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Response duration (MCL cohort) [ Time Frame: From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years ]
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • PFS (MCL cohort) [ Time Frame: Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years ]
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • OS (MCL cohort) [ Time Frame: Time from the first dose of the study drug until death, assessed up to 3 years ]
    Responses are defined according the revised response criteria for malignant lymphoma. Summarized using standard Kaplan-Meier methods.
  • Incidence of adverse events (AEs), assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria [ Time Frame: Up to 30 days post-treatment ]
    Same as current

    Information By: Ohio State University Comprehensive Cancer Center

    Dates:
    Date Received: November 4, 2014
    Date Started: March 12, 2015
    Date Completion:
    Last Updated: April 3, 2017
    Last Verified: April 2017