Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01134341|
Recruitment Status : Completed
First Posted : June 2, 2010
Last Update Posted : December 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cutaneous T-cell Lymphoma Mycosis Fungoides Sezary Syndrome Primary Cutaneous Anaplastic Large Cell Lymphoma||Drug: Pralatrexate Injection Drug: Bexarotene Capsules Dietary Supplement: Vitamin B12 Dietary Supplement: Folic Acid||Phase 1|
This is a multi-center, dose-finding, Phase 1 study of pralatrexate plus bexarotene in patients who have relapsed or refractory CTCL.
• 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.
- 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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-label, Dose-finding Study of Pralatrexate Plus Systemic Bexarotene in Patients With Relapsed or Refractory Cutaneous T Cell Lymphoma|
|Study Start Date :||March 2010|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
Experimental: 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.
Drug: 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.
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.
Dietary Supplement: 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).
Other Name: Cyanocobalamin
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).
- Dose Limiting Toxicity (DLT) Rate [ Time Frame: Assessed weekly through cycle 1 (weeks 1-4) ]DLT rate is the number of patients experiencing a DLT divided by number of evaluable patients and it will be summarized by dose level.
- Overall Response Rate (ORR) [ Time Frame: Assessed after every 2 cycles (8 weeks) for the first 12 months, then every 4 cycles (16 weeks) until progression of disease. ]
best overall response is the best response recorded from the start of treatment until PD.
The objective response rate is the proportion of patients with a best overall response of either CR or PR and it will be summarized by dose level and overall.
- Number of Patients with Treatment-related Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: Recorded at all study visits: weekly (every 7 +/- 2 days) while on treatment and at safety follow-up (35 +/- 5 days post-last dose) or early termination visit (at time of withdrawal). ]
(CTCAE) Scale, Version 4.0 for AE grading.
- Grade 3 neutropenia lasting for ≥ 7 days or granulocyte colony-stimulating factor (G-CSF) administered.
- Grade 3 thrombocytopenia.
- Grade 3 treatment-related hyperlipidemia or hypothyroidism
- Grade 3 study treatment-related non-hematologic toxicity
- Pharmacokinetic Parameters [ Time Frame: Sampling through 24 hours post end-injection of pralatrexate in cycle 1 dose 1 (week 1) and cycle 1 dose 3 (week 3). ]This was collected during the dose-finding stage of the study. PK sampling is not included in the cohort expansion.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01134341
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, Pennsylvania|
|University of Pittsburgh School of Medicine|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Ospedale Sant'Orsola - Policlinico Sant'Orsola|
|Bologna, Italy, 40138|
|Study Director:||Pankaj Sharma, MD||Spectrum Pharmaceuticals, Inc|