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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01134341
First received: May 28, 2010
Last updated: February 11, 2014
Last verified: February 2014

May 28, 2010
February 11, 2014
March 2010
June 2014   (final data collection date for primary outcome measure)
Dose Limiting Toxicity (DLT) Rate [ Time Frame: Assessed weekly through cycle 1 (weeks 1-4) ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01134341 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
  • 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). ] [ Designated as safety issue: Yes ]
  • 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). ] [ Designated as safety issue: Yes ]
    This was collected during the dose-finding stage of the study. PK sampling is not included in the cohort expansion.
  • 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. ] [ Designated as safety issue: No ]
  • Incidence of Treatment-related Adverse Events (AEs), Serious Adverse Events (SAEs), and Treatment Discontinuations due to AEs [ 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). ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic Parameters [ Time Frame: Sampling through 72 hours post end-injection of pralatrexate in cycle 1 dose 1 (week 1) and cycle 1 dose 3 (week 3). ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma
A Phase 1, Open-label, Dose-finding Study of Pralatrexate Plus Systemic Bexarotene in Patients With Relapsed or Refractory Cutaneous T Cell Lymphoma

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cutaneous T-cell Lymphoma
  • Mycosis Fungoides
  • Sezary Syndrome
  • Primary Cutaneous Anaplastic Large Cell Lymphoma
  • 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.

    Other Names:
    • FOLOTYN
    • PDX
    • Pralatrexate
    • (RS)-10-propargyl-10-deazaaminopterin
  • 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.

    Other Names:
    • Bexarotene
    • Targretin®
  • 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).

    Other Names:
    • Vitamin B9
    • Folate
    • Folacin
Experimental: Pralatrexate & Bexarotene
Interventions:
  • Drug: Pralatrexate Injection
  • Drug: Bexarotene Capsules
  • Dietary Supplement: Vitamin B12
  • Dietary Supplement: Folic Acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
42
December 2014
June 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Italy
 
NCT01134341
PDX-018
Not Provided
Spectrum Pharmaceuticals, Inc
Spectrum Pharmaceuticals, Inc
Not Provided
Study Director: Pankaj Sharma, MD Spectrum Pharmaceuticals, Inc
Spectrum Pharmaceuticals, Inc
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP