Clinical Trial: An Investigational Study Drug, Palbociclib (PD-0332991), Is Being Studied In Patients With Mantle Cell Lymphoma. Patients Must Have Received Prior Treatment(s) For Mantle Cell Lymphoma.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study Of Pd 0332991 In Patients With Previously Treated Mantle Cell Lymphoma

Brief Summary: This is a pilot study evaluating tumor activity using Positron Emission Tomography, which is also known as a "PET scan". This study will assess the safety of using PD-0332991 in patients with mantle cell lymphoma.

Detailed Summary:
Sponsor: Pfizer

Current Primary Outcome:

  • Correlation Coefficient Between Change From Baseline in Fluoro-L-thymidine Positron Emission Tomography (FLT-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [ Time Frame: Baseline, Cycle 1 Day 21 ]
    Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Change from baseline in [(18)F]-FLT-PET SUVmax at Cycle 1 Day 21 and change from baseline in Phospho-Rb percent positive cells at Cycle 1 Day 21 were analyzed. The change values of FLT-PET SUVmax and Phospho-Rb percent positive cells were then correlated. Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.
  • Correlation Coefficient Between Change From Baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Maximum Standard Uptake Value (SUVmax) and in Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [ Time Frame: Baseline, Cycle 1 Day 21 ]
    Maximum standard uptake value (SUVmax) was defined as the maximum value attained for the ratio of tissue radioactivity concentration at any time and the injected radioactivity concentration divided by the body weight (in kilogram [kg]). Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique. Chang

    Original Primary Outcome: To evaluate the use of PET as an assessment of target modulation. To assess the overall safety profile characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events and any laboratory abnormalities.

    Current Secondary Outcome:

    • Progression-Free Survival (PFS) [ Time Frame: Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) ]
      PFS was defined as the time from first dose of study medication to the first documentation of objective tumor progression, or to death due to any cause, whichever occurred first. Tumor progression was defined as >50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease. PFS= (first event date minus the first dose date plus 1) divided by 30.44.
    • Percentage of Participants With Objective Response [ Time Frame: Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) ]
      OR is defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR). Confirmed responses are those that persist on repeat imaging study 4 weeks after initial documentation of response. Complete response (CR)= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration; Partial response (PR)= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease.
    • Duration of Response (DR) [ Time Frame: Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) ]
      Time in months from first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to objective tumor progression (PD) or death due to any cause. DR= (date of first documentation of PD or death, minus the date of first CR or PR plus 1) divided by 30.44. CR= disappearance of all detectable clinical/radiographic evidence of disease, disease related symptoms present before start of therapy and biochemical abnormalities attributable to disease, nodal masses regressed to normal size, if spleen and bone marrow were involved, spleen regressed to normal size and not palpable and clear infiltrate on repeated bone marrow aspiration. PR= dominant nodes decreased by >50% in sum of products of diameters (SPD), no increase in size of other nodes/liver/spleen, lesions in organs (spleen/liver) regressed by >50% in SPD, no new sites of disease. PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease.
    • Time to Tumor Progression (TTP) [ Time Frame: Screening until tumor progression or death, assessed on Day 1 of every alternate cycle starting from Cycle 1 up to end of treatment (Day 609) or early withdrawal (if not completed during last 6 weeks) ]
      Time in months from date of first dose of study medication to first documentation of objective tumor progression (PD). TTP= (last known progression-free date minus date of first dose of study medication plus 1) divided by 30.44. PD was defined as greater than 50% increase in sum of products of diameters, of dominant nodes and documented non-nodal sites or appearance of new sites of disease.
    • Correlation Coefficient Between Plasma PD 0332991 Concentration and Change From Baseline in Biomarkers and SUVmax at Cycle 1 Day 21 [ Time Frame: Baseline, Cycle 1 Day 21 ]
      Plasma PD 0332991 concentration at Cycle 1 Day 21 was analyzed. Change from baseline in biomarkers (Ki-67 composite score, Cyclin D1 composite score, phospho-Rb positive cells) and SUVmax (FLT-PET SUVmax, FDG-PET SUVmax) at Cycle 1 Day 21 were analyzed. Correlation between PD 0332991 concentration and change in biomarkers (concentration versus Ki-67, concentration versus Cyclin, and concentration versus phospho-Rb) and SUVmax (concentration versus FLT-PET SUVmax, concentration versus FDG-PET SUVmax) was then assessed. Composite score = (sum of each intensity category multiplied by percent of cells in that category). Intensity categories of staining (0 = no staining; 1 = weak staining; 2 = moderate staining; 3 = strong staining). Here, 'N' (number of participants analyzed) signifies participants evaluable for this measure.


    Original Secondary Outcome: Evaluate efficacy with diseases assessments: Progression Free Survival (PFS), Overall Response Rate (ORR), Duration of Response (DR), and ï Time to Tumor Progression (TTP). Explore potential PD-0332991 concentration-effect relationships.

    Information By: Pfizer

    Dates:
    Date Received: January 5, 2007
    Date Started: May 2007
    Date Completion:
    Last Updated: October 6, 2015
    Last Verified: October 2015