Trial of PD 0332991 Plus Bortezomib in Patients With Relapsed Mantle Cell Lymphoma

NCT01111188 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 0903010300
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Mantle cell lymphoma (MCL) is characterized by cell cycle dysregulation. PD 0332991 is a cyclin-dependent kinase 4 and 6 inhibitor capable of inhibiting cell cycling of MCL. A phase I study has demonstrated the safety and anti-lymphoma activity of PD 0332991. Bortezomib is a first generation proteasome inhibitor approved for treatment of patients with recurrent MCL. Preclinical data suggests that PD 0332991 and bortezomib may act synergistically in MCL. PD 0332991 will be administered continuously for 12 days followed by a 9 day period without treatment. Bortezomib will be administered by intravenous bolus on days 8, 11, 15, and 18 of each cycle. One cycle is defined as three weeks. A maximum of ten cycles will be administered.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Determination of maximum tolerated dose (MTD) of PD 0332991 in combination with bortezomib in patients with recurrent mantle cell lymphoma

  MTD will be determined by occurrence of Dose Limiting Toxicities during the first cycle: * Any treatment-related grade 3 or 4 non-hematologic toxicity (except alopecia) * Delay in the administration of cycle 2 by more than one week due to treatment-related grade 4 neutropenia or thrombocytopenia or treatment-related grade 3-4 non-hematologic toxicity.

  Days 1-21 of treatment

Study Arms (1)

all subjects

EXPERIMENTAL

Subjects will receive PD 0332991 plus bortezomib. The dose of each agent will be dependent on the time point the subject enters the trial.

Drug: PD 0332991; Drug: bortezomib

Interventions

PD 0332991 DRUG

PD 0332991 will be given on Days 1-12 followed by 9 days of non-treatment in a 21-day cycle. Dose will depend on dose escalation schedule. (-3a) 50 mg (-3) 50 mg (-2)75 mg (-1)75 mg (1)100 mg (2)125 mg (3)125 mg (3a)100 mg

Also known as: Palbociclib

all subjects

bortezomib DRUG

Given as intravenous bolus on days 8, 11, 15, and 18 of 21-day cycle. Dose depends on dose-escalation schedule. (-3a)1.0 mg/m2 (-3) 0.7 mg/m2 (-2) 0.7 mg/m2 (-1) 1.0 mg/m2 ( 1) 1.0 mg/m2 ( 2) 1.0 mg/m2 ( 3) 1.3 mg/m2 (3a)1.3 mg/m2

Also known as: Velcade

all subjects

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization. All patients must have either a demonstrated t(11;14) by karyotype, fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1.
• Subjects must have measurable disease, defined as at least one tumor mass of \> 1.5 cm in diameter.
• Subjects must have received at least one prior chemotherapy-containing regimen and at least one prior rituximab-containing regimen.
• Age \> = 18 years.
• Accessible disease, defined as at least one of the following:
• Adenopathy accessible to core needle biopsy
• Bone marrow involvement
• Circulating lymphoma cells in the peripheral blood
• ECOG performance status \< = 2
• Patients must have normal organ and marrow function as defined below within 14 days before enrollment:
• ANC \> = 750 cells/uL
• platelets \> = 75,000 cells/uL
• Hemoglobin \> = 8.0 g/dL
• total bilirubin \< = 1.5 times upper limit of normal
• AST(SGOT)/ALT(SGPT) \< = 3 times upper limit of normal

You may not qualify if:

• Patients who have had chemotherapy, radiotherapy, antibodies, or investigational agents within 4 weeks prior to entering the study unless progression has been documented while on treatment, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients may be receiving prednisone at a maximum dose of 10 mg/day orally, provided the dose has been stable during the prior two weeks before starting treatment.
• Patients may not be receiving any other investigational agents.
• Prior exposure to PD 0332991
• Prior exposure to bortezomib will only be permitted if there was a documented complete or partial response and progression occurred off therapy
• Patients must not have experienced significant hematologic (grade 4) or neuropathic toxicities (grade 3 or 4) due to prior bortezomib therapy
• Peripheral neuropathy \> = grade 2 (CTCAEv3.0) within 14 days before enrollment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib (e.g. boron or mannitol).
• Contraindication to serial core needle biopsies
• Known HIV infection
• Known malabsorption syndrome that may affect absorption of the drug
• Known or suspected CNS involvement
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• QTc \> 470 msec
• Current use or anticipated need for food or drugs that are known potent CYP3A4 inhibitors, including their administration within 7-days prior to the first PD 0332991dose (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, nefazodone, diltiazem, atazanavir, amprenavir,and fosamprenavir)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Pfizer: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (1)

• Martin P, Ruan J, Furman R, Rutherford S, Allan J, Chen Z, Huang X, DiLiberto M, Chen-Kiang S, Leonard JP. A phase I trial of palbociclib plus bortezomib in previously treated mantle cell lymphoma. Leuk Lymphoma. 2019 Dec;60(12):2917-2921. doi: 10.1080/10428194.2019.1612062. Epub 2019 May 23.

  PMID: 31120355 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

palbociclib; Bortezomib

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• John P Leonard, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: April 27, 2010
• Study Start: August 23, 2010
• Primary Completion: February 26, 2013
• Study Completion: April 12, 2019
• Last Updated: June 27, 2019

Record last verified: 2019-06

Locations

US (1)