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.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00420056
First received: January 5, 2007
Last updated: May 25, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Lymphoma, Mantle-Cell
Drug: PD-0332991
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study Of Pd 0332991 In Patients With Previously Treated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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]-FDG-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.

  • Change From Baseline in Maximum Standard Uptake Value (SUVmax) at Cycle 1 Day 21 [ Time Frame: Baseline, Cycle 1 Day 21 ] [ Designated as safety issue: No ]
    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]). Change from baseline in SUVmax was assessed using [(18)F]-FLT-PET and [(18)F]-FDG-PET techniques.

  • Correlation Between Positron Emission Tomography (PET) Response and Progression-Free Survival (PFS) [ Time Frame: Baseline, Cycle 1 Day 21 for PET response; 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) for PFS ] [ Designated as safety issue: No ]
    PET response was defined as complete response (CR) = mean SUVmax same as of background; partial response (PR) = mean SUVmax less than (<) 75 percent (%) of baseline; progressive disease (PD) = mean SUVmax greater than (>) 125% of baseline; stable disease (SD) = mean SUVmax greater than or equal to (>=) 75% of baseline and mean SUVmax less than or equal to (<=) 125% of baseline. 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.

  • Correlation Between Positron Emission Tomography (PET) Response and Objective Response (OR) [ Time Frame: Baseline, Cycle 1 Day 21 for PET response; 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) for OR ] [ Designated as safety issue: No ]
    OR: CR= disappearance of all clinical/radiographic evidence of disease, disease related symptoms and biochemical abnormalities, 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 repeat 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 regressed by >50% in SPD, no new sites of disease; SD= response <PR and no PD, documented >=1 time after start of therapy, no new sites of disease; PD= >50% increase in SPD of dominant nodes and other nodes or appearance of new sites of disease. PET response: CR= mean SUVmax same as background; PR= mean SUVmax <75% of baseline; PD= mean SUVmax >125% of baseline; SD= mean SUVmax >=75% of baseline but <=125% of baseline. Correlation was reported as conjoint number of participants with PET response at Cycle 1 Day 21 and OR at end of study.

  • Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.

  • Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 ] [ Designated as safety issue: No ]
    Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.

  • Ki-67 Composite Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. 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). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

  • Ki-67 Composite Score at Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 ] [ Designated as safety issue: No ]
    Percentage of Ki-67 positive cells was determined by Immunohistochemical staining technique. 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). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

  • Cyclin D1 Composite Score at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. 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). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

  • Cyclin D1 Composite Score at Cycle 1 Day 21 [ Time Frame: Cycle 1 Day 21 ] [ Designated as safety issue: No ]
    Percentage of Cyclin D1 positive cells was determined by Immunohistochemical staining technique. 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). Composite score ranges from 0 (no staining) to 300 (100% of cells with 3 staining intensity).

  • Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to 28 days after last dose of study medication ] [ Designated as safety issue: Yes ]
    Criteria for laboratory test abnormality: Hematology (Hemoglobin [<0.8*lower limit of normal {LLN}], Platelets [<0.5*LLN/ >1.75*upper limit of normal {ULN}], White blood cells [<0.6*LLN/ >1.5*ULN], Lymphocytes, Neutrophils [<0.8*LLN/ >1.2*ULN], Basophils, Eosinophils, Monocytes [>1.2*ULN]); Liver Function (Total bilirubin [>1.5*ULN], Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Alkaline phosphatase [>0.3*ULN], Total protein, Albumin [<0.8*LLN/ >1.2*ULN]); Renal Function (Blood urea nitrogen, Creatinine [>1.3*ULN], Uric acid [>1.2*ULN]); Electrolytes (sodium [<0.95*LLN/ >1.05*ULN], potassium, chloride, calcium, magnesium [<0.9*LLN/ >1.1*ULN], phosphate [<0.8*LLN/ >1.2*ULN]); Other (Glucose [<0.6*LLN/ >1.5*ULN]).

  • Number of Participants With Treatment-Emergent Adverse Events by Severity [ Time Frame: Day 1 up to 28 days after last dose of study medication ] [ Designated as safety issue: Yes ]
    AE = any untoward medical occurrence in participant who received study medication without regard to possibility of causal relationship. Severity was assessed as: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe) = unacceptable or intolerable events, significantly interrupting usual daily activity, and requiring systemic medication therapy/other treatment; Grade 4 (Life-threatening) = events causing participant to be in imminent danger of death; Grade 5 (Death) = death related to an AE. Treatment-emergent events = between first dose of study medication and up to 28 days after last dose, that were absent before treatment or that worsened relative to pre-treatment state. A participant may be represented in more than 1 category.

  • Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 up to 28 days after last dose of study medication ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The events which were considered treatment-related by sponsor and/or investigator were reported.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 17
Study Start Date: May 2007
Study Completion Date: March 2012
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PD-0332991 Drug: PD-0332991
125 mg, oral, Days 1-21 of a 28-day cycle

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented MCL.
  • Must have received at least one prior therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
  • Adequate organ function as outlined in the protocol.

Exclusion Criteria:

  • Major surgery, radiation therapy, or systemic therapy within 4 weeks of study enrollment.
  • Prior radiation therapy to >25% of the bone marrow (whole pelvis is 25%).
  • Uncontrolled brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00420056

Locations
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
New York Presbyterian Hospital
New York, New York, United States, 10021
Weill Medical College of Cornell University - New York Presbyterian Hospital
New York, New York, United States, 10021
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00420056     History of Changes
Other Study ID Numbers: A5481002
Study First Received: January 5, 2007
Results First Received: March 4, 2015
Last Updated: May 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 30, 2015