An Investigational Drug, Palbociclib (PD-0332991), Is Being Studied In Combination With Velcade And Dexamethasone In Patients With Multiple Myeloma. Patients Must Have Received Prior Treatment For Multiple Myeloma.

NCT00555906 | Completed Phase 2 Results

• 2 other identifiers: A54810042010-022515-20
• Study Type: interventional
• Target: 53
• Locations: 3 countries
• Sites: 19

Brief Summary

This is a Phase 1/2 study evaluating the safety and anti-tumor activity of PD 0332991 in combination with Velcade® \[bortezomib\] and dexamethasone in patients who have received at least one previous treatment for multiple myeloma.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1

  MTD=highest dose level for which no more than 1 out of 6 participants experienced dose-limiting toxicity (DLT). DLT=any of the following treatment-related events: Absolute neutrophil count (ANC) less than (\<)1000/microliter (mcL) (Grade 3 neutropenia) associated with documented infection/fever \>=38.5degrees Celsius (C); Grade \>=3 nonhematologic treatment-related toxicity, except those that were not maximally treated or considered tolerable, Grade 3 corrected QT interval (QTc) prolongation (QTc \>500 millisecond \[msec\]) in asymptomatic participants even after repeat testing to exclude confounding factors and correction of reversible causes; Delay in the administration of Cycle 2 for more than 1 week of the planned date due to platelet count \<25,000/mcL and/or ANC \<500/mcL, or due to prolonged nonhematologic toxicities of Grade \>=3; Inability to deliver at least 80 percent (%) of the planned PD 0332991 or bortezomib doses during Cycle 1 due to toxicity.

  Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B

• Recommended Phase II Dose (RP2D) of PD-0332991: Phase 1

  RP2D was determined based on the MTD, safety and tolerability profile of the study treatment.

  Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B

• Percentage of Participants With Objective Response (OR): Phase 2

  OR: confirmed stringent complete response(sCR),complete response(CR),very good partial response(VGPR) or partial response(PR) as per International Myeloma Working Group Uniform Response Criteria (IMWGURC). sCR: normal serum free light chain (FLC) ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, \<5 percent (%) plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, \>= 90% reduction in serum M-protein, \<100 mg/24 hour (hr) urine M-protein. PR: \>=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by \>=90% or to \<200 mg/24 hr, \>=50% decrease in difference between involved and uninvolved FLC levels if serum, urine M-protein were unmeasurable, \>= 50% reduction in plasma cells, provided baseline bone marrow plasma cell was \>=30% if serum, urine M-protein were unmeasurable and serum free light assay was unmeasureable.

  Cycle 1 Day 1 (baseline) up to end of study (up to cycle 22 for schedule B)

Secondary Outcomes (12)

• Percent Change From Screening in Phosphorylated Retinoblastoma (Rb), Tumor Biomarkers and Soluble Biomarkers Levels: Phase 1

  Screening, C1D1(baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)

• Best Overall Response: Phase 1

  Cycle 1 Day 1 (baseline), assessed on Day 1 of every cycle up to end of study (up to Cycle 22 for schedule A and schedule B)

• Time to Tumor Progression (TTP): Phase 2

  Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

• Progression-free Survival (PFS): Phase 2

  Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

• Duration of Objective Response (DR): Phase 2

  Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Study Arms (1)

1

EXPERIMENTAL

Drug: Bortezomib; Drug: Dexamethasone; Drug: PD 0332991

Interventions

Bortezomib DRUG

Escalating doses of bortezomib will be administered intravenously on Days 8, 11, 15 and 18 of a 28-day cycle (Schedule A) or of a 21-day cycle (Schedule B). The planned doses to be evaluated are 0.7, 1 and 1.3 mg/m2 in combination with PD 0332991 and dexamethasone.

Also known as: Velcade

1

Dexamethasone DRUG

20 mg, orally on Days 8, 11, 15 and 18 of a 28 day cycle (Schedule A) or of a 21-day cycle (Schedule B) in combination with PD 0332991 and bortezomib.

1

PD 0332991 DRUG

Escalating doses of PD 0332991 will be administered orally on Days 1-21 of a 28-day cycle for Schedule A and on Days 1-12 of a 21-day cycle for Schedule B. The planned doses to be evaluated are 50, 75, 100 mg and 125 mg once daily in combination with bortezomib and dexamethasone.

1

Eligibility Criteria

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

You may qualify if:

• Diagnosis of symptomatic multiple myeloma as defined by International Myeloma Working Group (IMWGURC).
• Phase 1: Relapsed or relapsed/refractory myeloma after at least 1 previous treatments and with a life expectancy of more than 3 months.
• Phase 2: Measurable (as defined by IMWGURC) disease after at least 1 previous treatment.

You may not qualify if:

• History of allogeneic stem cell transplant.
• Phase 2 only: Prior bortezomib therapy will only be allowed if there was a demonstrated positive response, and disease progression occurred off therapy.
• Must have not experienced significant blood level changes, e.g. very low platelets, while on previous bortezomib therapy
• Prior radiation therapy to \> 25% of the bone marrow (whole pelvis is 25%).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (19)

Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611, United States

Location

Northwestern Memorial Hospital/Main Labs

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, 66205, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110-1093, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

New York Presbyterian, Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Related Publications (1)

• Niesvizky R, Badros AZ, Costa LJ, Ely SA, Singhal SB, Stadtmauer EA, Haideri NA, Yacoub A, Hess G, Lentzsch S, Spicka I, Chanan-Khan AA, Raab MS, Tarantolo S, Vij R, Zonder JA, Huang X, Jayabalan D, Di Liberto M, Huang X, Jiang Y, Kim ST, Randolph S, Chen-Kiang S. Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leuk Lymphoma. 2015;56(12):3320-8. doi: 10.3109/10428194.2015.1030641. Epub 2015 May 15.

  PMID: 25813205 DERIVED

Related Links

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

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2007
• First Posted: November 9, 2007
• Study Start: January 1, 2008
• Primary Completion: August 1, 2012
• Study Completion: March 1, 2013
• Last Updated: March 19, 2015
• Results First Posted: March 19, 2015

Record last verified: 2015-03

Locations

US (16); CZ (1); DE (2)