Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma

NCT ID: NCT01134341

Last Updated: 2019-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2015-08-31

Brief Summary

This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.

Detailed Description

This is a multi-center, dose-finding, Phase 1 study of pralatrexate plus bexarotene in patients who have relapsed or refractory CTCL.

Primary Objective(s):

• Determine the maximum tolerated dose (MTD) and recommended dose of pralatrexate plus bexarotene with concurrent vitamin B12 and folic acid supplementation when administered to patients who have failed prior systemic treatment.

Secondary Objective(s):

• Determine the safety profile of pralatrexate plus bexarotene when administered to patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL).
• Collect preliminary efficacy data.
• Determine the pharmacokinetic (PK) profile of pralatrexate plus bexarotene in patients who underwent plasma PK sampling

Conditions

Cutaneous T-cell Lymphoma; Mycosis Fungoides; Sezary Syndrome; Primary Cutaneous Anaplastic Large Cell Lymphoma

Keywords

Relapsed; Refractory

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bexarotene (Targretin) & Pralatrexate (Folotyn)

Bexarotene (Targretin): administered po qd. The initial daily dose of bexarotene will depend on the cohort to which each patient is assigned. Bexarotene will be self-administered except in patients who underwent plasma PK sampling on cycle 1, dose 1 and cycle 1, dose 3, at which time bexarotene was to be administered at the investigational site 1 hour (± 5 minutes) prior to pralatrexate administration.

Pralatrexate (Folotyn): administered weekly via IV push over a minimum of 30 seconds up to a maximum of 5 minutes. One cycle is 4 weeks in duration consisting of weekly dosing of pralatrexate for 3 weeks followed by 1 week of rest. The initial dose of pralatrexate will depend on the cohort to which each patient is assigned.

Group Type: EXPERIMENTAL

Pralatrexate Injection

Intervention Type: DRUG

Intravenous (IV) push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride).

10 or 15 mg/m2, depending on cohort assignment.

Dose reductions allowed for protocol-specified criteria.

Administered weekly for 3 weeks of 4-week cycle (weekly for 3 weeks with one week of rest) until criteria for discontinuation per the protocol are met.

Bexarotene Capsules

Intervention Type: DRUG

150 or 300 mg orally, depending on cohort assignment. Provided as 75 mg capsules and taken with a meal.

Dose reductions allowed for protocol-specified criteria and implemented per the Targretin® package insert.

Administered daily until criteria for study treatment discontinuation per the protocol are met.

Vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

1 mg intramuscular injection

Administered within 10 weeks prior to start of study treatment, every 8-10 weeks throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

1-1.25 mg orally

Administered daily for at least 7 days prior to start of study treatment, throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).

Interventions

Pralatrexate Injection

Intravenous (IV) push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline (0.9% sodium chloride).

10 or 15 mg/m2, depending on cohort assignment.

Dose reductions allowed for protocol-specified criteria.

Administered weekly for 3 weeks of 4-week cycle (weekly for 3 weeks with one week of rest) until criteria for discontinuation per the protocol are met.

Intervention Type: DRUG

Bexarotene Capsules

150 or 300 mg orally, depending on cohort assignment. Provided as 75 mg capsules and taken with a meal.

Dose reductions allowed for protocol-specified criteria and implemented per the Targretin® package insert.

Administered daily until criteria for study treatment discontinuation per the protocol are met.

Intervention Type: DRUG

Vitamin B12

1 mg intramuscular injection

Administered within 10 weeks prior to start of study treatment, every 8-10 weeks throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).

Intervention Type: DIETARY_SUPPLEMENT

Folic Acid

1-1.25 mg orally

Administered daily for at least 7 days prior to start of study treatment, throughout the study and for 30 days after last study treatment (dose of pralatrexate or bexarotene).

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

FOLOTYN; PDX; Pralatrexate; (RS)-10-propargyl-10-deazaaminopterin; Bexarotene; Targretin®; Cyanocobalamin; Vitamin B9; Folate; Folacin

Eligibility Criteria

Inclusion Criteria

• Cutaneous T-cell lymphoma patients with subtypes of mycosis fungoides (MF) Stage IB or higher, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma who have failed a previous systemic treatment.
• Patients must have received at least 1 previous systemic therapy, and either progressed or not tolerated their last prior treatment regimen.
• Eastern Cooperative Oncology Group Performance Status less than or equal to 2.
• Adequate blood, liver, and kidney function as defined by laboratory tests.
• Women of childbearing potential must practice medically acceptable contraception from study treatment start until at least 30 days after the last dose of study treatment. Negative serum pregnancy test within 14 days before the first day of study treatment (not required for patients who are postmenopausal for at least 1 year or surgically sterilized). Study treatment should not be given to women who are breastfeeding.
• Males who are sexually active must agree to practice medically acceptable barrier contraception while receiving study treatment and for 30 days after the last dose of study treatment.
• Give written informed consent & privacy authorization.

Exclusion Criteria

• If there is a history of prior malignancies other than non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, or localized thyroid cancer, patient must be disease free for at least 5 years. Patients with other prior malignancies less than 5 years before study entry may be enrolled if they received treatment resulting in complete resolution of the cancer and have no current clinical, radiologic, or laboratory evidence of active or recurrent disease.
• Human immunodeficiency virus (HIV)-positive diagnosis with a CD4 count of less than 100 mm3 or detectable viral load within the past 3 months, and receiving combination anti-retroviral therapy.
• Diagnosis of Hepatitis B virus, or Hepatitis C virus with detectable viral load or immunological evidence of chronic active disease or receiving/requiring antiviral therapy.
• Active central nervous system disease requiring treatment.
• Active uncontrolled infection, underlying medical condition, or other serious illness impairing the patient's ability to receive protocol treatment.
• Discontinuation of prior oral bexarotene due to an allergic reaction or treatment-related toxicity.
• Major surgery within 2 weeks of planned start of treatment.
• Conventional or investigational chemotherapy or radiation therapy encompassing greater than 10% of bone marrow within 4 weeks prior to study treatment.
• ECP, phototherapy with PUVA, or ultraviolet (UV) therapy within 2 weeks prior to study treatment.
• Systemic corticosteroids within 3 weeks of study treatment, unless patient has been taking a continuous dose of no more than 10 mg per day of prednisone or equivalent for at least 4 weeks.
• Initiation of or change in dosage of topical corticosteroids within 3 weeks of study treatment (topical steroid use within 3 weeks is allowed provided the strength and use has been stable for at least 4 weeks).
• Investigational drugs, biologics, or devices use within 2 weeks prior to study treatment or planned use during the study.
• Monoclonal antibody within 3 months without evidence of PD.
• Use of oral retinoids, except bexarotene, within 4 weeks of study treatment or high-dose vitamin A (once daily multi-vitamin allowed).
• Previous exposure to pralatrexate.
• Uncontrolled hypercholesterolemia or hypertriglyceridemia.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acrotech Biopharma Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pankaj Sharma, MD

Role: STUDY_DIRECTOR

Spectrum Pharmaceuticals, Inc

Locations

Stanford University School of Medicine

Stanford, California, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center

Houston, Texas, United States

Ospedale Sant'Orsola - Policlinico Sant'Orsola

Bologna, , Italy

Countries

United States; Italy

Other Identifiers

PDX-018

Identifier Type: -

Identifier Source: org_study_id