Lymphoma, Mantle-CellPhase 1NCT00420056

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.

A Phase 1 study testing PD-0332991 in people with Lymphoma, Mantle-Cell, run by Pfizer at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Lymphoma, Mantle-Cell
What is being tested?: PD-0332991
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 6 sitesUnited States
Study dates: May 2007to Mar 2012
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Brigham & Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
New York Presbyterian Hospital
New York, New York, 10021
Weill Medical College of Cornell University - New York Presbyterian Hospital
New York, New York, 10021
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

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

Conditions: Lymphoma, Mantle-Cell
Being tested: PD-0332991
Medical subject headings: Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PD-0332991Drug
125 mg, oral, Days 1-21 of a 28-day cycle

Study groups in NCT00420056
Study group	Role	What they receive
PD-0332991	Experimental	Not described Receives: Drug: PD-0332991

What is being measured

The primary outcome is the main question the study is designed to answer.

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
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.
Measured: Baseline, Cycle 1 Day 21
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
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.
Measured: Baseline, Cycle 1 Day 21
Change From Baseline in Maximum Standard Uptake Value (SUVmax) at 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.
Measured: Baseline, Cycle 1 Day 21
Correlation Between Positron Emission Tomography (PET) Response and Progression-Free Survival (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.
Measured: 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
Correlation Between Positron Emission Tomography (PET) Response and Objective Response (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.
Measured: 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
Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at Baseline
Phosphorylation of retinoblastoma (Rb) protein in the tumor cells, expressed as phospho-Rb percent positive cells, was assessed using Immunohistochemical staining technique.
Measured: Baseline
Phosphorylated Retinoblastoma (Phospho-Rb) Percent Positive Cells at 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.
Measured: Cycle 1 Day 21
Ki-67 Composite Score at 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).
Measured: Baseline
Ki-67 Composite Score at 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).
Measured: Cycle 1 Day 21
Cyclin D1 Composite Score at 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).
Measured: Baseline
Cyclin D1 Composite Score at 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).
Measured: Cycle 1 Day 21
Number of Participants With Laboratory Test Abnormalities
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]).
Measured: Baseline up to 28 days after last dose of study medication
Number of Participants With Treatment-Emergent Adverse Events by Severity
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.
Measured: Day 1 up to 28 days after last dose of study medication
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Measured: Day 1 up to 28 days after last dose of study medication

Secondary outcomes (5)

Progression-Free Survival (PFS)
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.
Measured: 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)
Percentage of Participants With Objective Response
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.
Measured: 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)
Duration of Response (DR)
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.
Measured: 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 to Tumor Progression (TTP)
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.
Measured: 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)
Correlation Coefficient Between Plasma PD 0332991 Concentration and Change From Baseline in Biomarkers and SUVmax at 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.
Measured: Baseline, Cycle 1 Day 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Mar 2012

First posted9 Jan 2007 (estimated)
Study startMay 2007
Primary completionMar 2010
Study completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Lymphoma, Mantle-CellStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00420056
Sponsor's protocol ID: A5481002
Status last verified: Oct 2015
First submitted: 5 Jan 2007
Last updated: 28 Oct 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Leonard JP, LaCasce AS, Smith MR, Noy A, Chirieac LR, Rodig SJ, Yu JQ, Vallabhajosula S, Schoder H, English P, Neuberg DS, Martin P, Millenson MM, Ely SA, Courtney R, Shaik N, Wilner KD, Randolph S, Van den Abbeele AD, Chen-Kiang SY, Yap JT, Shapiro GI. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood. 2012 May 17;119(20):4597-607. doi: 10.1182/blood-2011-10-388298. Epub 2012 Mar 1.
PubMed 22383795

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer

All Lymphoma, Mantle-Cell trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study Of Pd 0332991 In Patients With Previously Treated Mantle Cell Lymphoma
ClinicalTrials.gov ID: NCT00420056
Acronym / sponsor ID: A5481002
Conditions: Lymphoma, Mantle-Cell
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: May 2007
Primary completion: Mar 2010 (actual)
Study completion: Mar 2012 (actual)
First posted: 9 Jan 2007 (estimated)
Results: Posted 9 Jun 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
PD-0332991	Experimental	Drug: PD-0332991

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PD-0332991125 mg, oral, Days 1-21 of a 28-day cycle	Drug	PD-0332991

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. 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
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
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
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
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
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
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
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
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
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
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
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
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.

5 secondary outcomes

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)
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)
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 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)
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

Results and safety

Results posted to the registry on 9 Jun 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PD 0332991	17	0

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. Number. Unit: correlation coefficient

Measure	PD 0332991 n = 10
Value	-0.25034

PD 0332991: p = 0.4854, Regression, Linear

Population analysed: SUVmax was analyzed using imaging analysis set (participants in FAS who completed baseline \[(18)F\]-fluorodeoxyglucose PET \[FDG-PET\] and \[(18)F\]-FLT-PET, and at least 1 on-treatment \[Day 21\] PET) and phospho-Rb was analyzed using tumor analysis set (participants in FAS who completed tumor biomarker assessments at baseline and Day 21).

Primary outcome: 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. Number. Unit: correlation coefficient

Measure	PD 0332991 n = 10
Value	0.13551

PD 0332991: p = 0.7090, Regression, Linear

Population analysed: SUVmax was analyzed using imaging analysis set (participants in FAS who completed baseline \[(18)F\]-FDG-PET and \[(18)F\]-FLT-PET, and at least 1 on-treatment \[Day 21\] PET) and phospho-Rb was analyzed using tumor analysis set (participants in FAS who completed tumor biomarker assessments at baseline and Day 21).

Primary outcome: Change From Baseline in Maximum Standard Uptake Value (SUVmax) at Cycle 1 Day 21

Time frame: Baseline, Cycle 1 Day 21. Mean (Standard Deviation). Unit: standard uptake value (SUV)

Measure	PD 0332991 n = 17
Baseline: FLT-PET	9.964 (4.929)
Baseline: FDG-PET	9.049 (4.654)
Change at Cycle 1 Day 21: FLT-PET	-4.551 (2.968)
Change at Cycle 1 Day 21: FDG-PET	-2.271 (2.913)

Population analysed: Imaging analysis set included participants in FAS who completed baseline \[(18)F\]-FDG-PET and \[(18)F\]-FLT-PET, and at least 1 on-treatment (Day 21) PET.

Primary outcome: 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

Population analysed: Analysis for this outcome measure was not run as there were so few responders.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
PD 0332991	3 of 17 (17.6%)	17 of 17 (100%)	Not reported

Limitations and caveats (from the sponsor): Results are reported for change from baseline in maximum standard uptake value (SUVmax) instead of percent change from baseline in SUVmax.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22383795Leonard JP, LaCasce AS, Smith MR, Noy A, Chirieac LR, Rodig SJ, Yu JQ, Vallabhajosula S, Schoder H, English P, Neuberg DS, Martin P, Millenson MM, Ely SA, Courtney R, Shaik N, Wilner KD, Randolph S, Van den Abbeele AD, Chen-Kiang SY, Yap JT, Shapiro GI. Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood. 2012 May 17;119(20):4597-607. doi: 10.1182/blood-2011-10-388298. Epub 2012 Mar 1.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.

Related trials for Lymphoma, Mantle-Cell

Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PD-0332991 in people with Lymphoma, Mantle-Cell, run by Pfizer at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00420056, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015.