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
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) Rate [ Time Frame: Assessed weekly through cycle 1 (weeks 1-4) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 42
Study Start Date: March 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pralatrexate & Bexarotene 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01134341

Locations
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
Italy
Ospedale Sant'Orsola - Policlinico Sant'Orsola
Bologna, Italy, 40138
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Pankaj Sharma, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01134341     History of Changes
Other Study ID Numbers: PDX-018
Study First Received: May 28, 2010
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency

Keywords provided by Spectrum Pharmaceuticals, Inc:
Relapsed
Refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Primary Cutaneous Anaplastic Large Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Folic Acid
Hydroxocobalamin
Vitamin B Complex
Vitamin B 12
Vitamins
10-deazaaminopterin
Bexarotene
Aminopterin
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014