Clinical trial NCT00555906: 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.
Official title: Phase 1/2 Open-label Study Of The Safety And Efficacy Of Pd 0332991 In Combination With Bortezomib And Dexamethasone In Patients With Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-11-09
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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%).

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1
timeFrame: Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B
measure: Recommended Phase II Dose (RP2D) of PD-0332991: Phase 1
timeFrame: Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B
measure: Percentage of Participants With Objective Response (OR): Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to end of study (up to cycle 22 for schedule B)
Secondary outcomes:
measure: Percent Change From Screening in Phosphorylated Retinoblastoma (Rb), Tumor Biomarkers and Soluble Biomarkers Levels: Phase 1
timeFrame: 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)
measure: Best Overall Response: Phase 1
timeFrame: 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)
measure: Time to Tumor Progression (TTP): Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: Progression-free Survival (PFS): Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: Duration of Objective Response (DR): Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: Overall Survival (OS): Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to end of study (up to Cycle 22 for schedule B), thereafter every 3 months until 1 year after the last dose of palbociclib
measure: Number of Participants With Adverse Events (AEs) by Severity: Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Medication: Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: Number of Participants With Laboratory Abnormalities: Phase 2
timeFrame: Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib
measure: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30): Phase 2
timeFrame: 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)
measure: Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20): Phase 2
timeFrame: 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)
measure: Modified Version of Brief Pain Inventory - Short Form (m-BPI-sf) Questionnaire: Phase 2
timeFrame: 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)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital/Main Labs
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center and Medical Pavilion
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York Presbyterian, Weill Cornell Medical College
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Praha 2
country: Czech Republic
facility: Vseobecna fakultni nemocnice v Praze
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Mainz
country: Germany
facility: Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.