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.

NCT00420056 | Completed Phase 1 Results

• 1 other identifier: A5481002
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 6

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.

Conditions

Lymphoma, Mantle-Cell

Outcome Measures

Primary Outcomes (14)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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).

  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).

  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).

  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 \[\<0.6\*LLN/ \>1.5\*ULN\]).

  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.

  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.

  Day 1 up to 28 days after last dose of study medication

Secondary Outcomes (5)

• 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)

• 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)

• 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 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)

• 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

Study Arms (1)

PD-0332991

EXPERIMENTAL

Drug: PD-0332991

Interventions

PD-0332991 DRUG

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

PD-0332991

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Weill Medical College of Cornell University - New York Presbyterian Hospital

New York, New York, 10021, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• 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.

  PMID: 22383795 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Results are reported for change from baseline in maximum standard uptake value (SUVmax) instead of percent change from baseline in SUVmax.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2007
• First Posted: January 9, 2007
• Study Start: May 1, 2007
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2012
• Last Updated: October 28, 2015
• Results First Posted: June 9, 2015

Record last verified: 2015-10

Locations

US (6)