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.
- Conditions
- Lymphoma, Mantle-Cell
- Interventions
- Drug: PD-0332991
- Registration Number
- NCT00420056
- Lead Sponsor
- Pfizer
- 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 Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PD-0332991 PD-0332991 -
- Primary Outcome Measures
Name Time Method 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 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 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 \[(18)F\]-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 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 \[kg\]). 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) 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 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) 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 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 Baseline 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 Cycle 1 Day 21 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 Baseline 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 Cycle 1 Day 21 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 Baseline 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 Cycle 1 Day 21 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 Baseline up to 28 days after last dose of study medication 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 Day 1 up to 28 days after last dose of study medication 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) Day 1 up to 28 days after last dose of study medication 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
Name Time Method Progression-Free Survival (PFS) 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 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) 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) 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 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.
Trial Locations
- Locations (6)
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Weill Medical College of Cornell University - New York Presbyterian Hospital
🇺🇸New York, New York, United States