Clinical Trial: Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL

Brief Summary: This phase I/II trial studies the side effects and the best dose of ofatumumab and dinaciclib and to see how well they work in treating patients with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-cell prolymphocytic leukemia. Monoclonal antibodies, such as ofatumumab, can find cancer cells and help kill them. Dinaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ofatumumab together with dinaciclib may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib (phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and B-cell prolymphocytic leukemia (B-PLL).

II. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in CLL/SLL/B-PLL.

III. To determine the overall response rate associated with this treatment as assessed by consensus response criteria. (Phase II)

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) after combination treatment with ofatumumab and dinaciclib.

II. To characterize the pharmacokinetics of dinaciclib when given in combination with ofatumumab.

III. To correlate pharmacokinetic features of dinaciclib with response, toxicity (particularly tumor lysis syndrome), and pharmacodynamic endpoints.

IV. To perform detailed baseline and serial pharmacodynamic studies of combination therapy with ofatumumab and dinaciclib and correlate these with response to therapy.

V. To correlate baseline disease-risk parameters (i.e., zeta-chain-associated protein kinase [ZAP]-70 expression, interphase cytogenetics, immunoglobulin heavy chain variable region [IgVH] mutational analysis, and other clinical prognostic factors) with response to therapy.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive ofatum
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum-tolerated dose of dinaciclib when given in combination with ofatumumab, defined as a dose level where at most one of 6 evaluable patients has a dose limiting toxicity (Phase Ia) [ Time Frame: Day 56 ]
    Graded according to the National Cancer Institute (NCI) CTCAE version (v)4.0. Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.
  • Number of dose-limiting toxicity incidents graded according to the NCI CTCAE v4.0 (Phase I) [ Time Frame: Up to day 56 ]
    Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE version 4 standard toxicity grading. Non-hematologic dose-limiting toxicities such as dyspnea and renal will be evaluated via the ordinal CTCAE standard toxicity grading only.
  • Proportion of patients who achieve an overall response, defined as achieving a complete response, an unconfirmed complete response (SLL only), or a partial response (Phase II) [ Time Frame: Up to 28 weeks ]
    Overall response rate and TLS rate will be evaluated and analyzed using proportions, where the number of those with any response will be divided by the number of evaluable subjects. Similarly, the number of subjects with TLS will be divided by the number of subjects who have had at least one day of treatment and are thus evaluable for toxicity. 95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed.

    Original Primary Outcome:

    • Maximum-tolerated dose (Phase I)
    • Number of dose-limiting toxicity incidents (Phase I)
    • Proportion of patients who achieve an overall response (Phase II)


    Current Secondary Outcome:

    • Complete response rate [ Time Frame: Up to 28 weeks ]
      95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed.
    • Overall survival [ Time Frame: Time from study entry to death due to any cause, assessed up to 5 years ]
      Distributions will be explored and assessed using the methods of Kaplan and Meier.
    • PFS [ Time Frame: Time from study entry to documentation of disease progression and/or death, assessed up to 5 years ]
      95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed. Distributions will be explored and assessed using the methods of Kaplan and Meier.
    • Time to treatment failure [ Time Frame: Time from study entry to the date patients end treatment, up to 28 weeks ]
      Distributions will be explored and assessed using the methods of Kaplan and Meier.


    Original Secondary Outcome:

    • Complete response rate
    • PFS
    • Overall survival
    • Time to treatment failure
    • Correlation between prognostic markers and response to therapy


    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: January 16, 2012
    Date Started: January 2012
    Date Completion:
    Last Updated: February 7, 2017
    Last Verified: February 2017