Cutaneous T-cell LymphomaPhase 1NCT01134341
Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma
A Phase 1 study testing Pralatrexate Injection, Bexarotene Capsules and Vitamin B12 in people with Cutaneous T-cell Lymphoma and Mycosis Fungoides, run by Acrotech Biopharma Inc. at 5 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome
- What is being tested?
- Pralatrexate Injection, Bexarotene Capsules and Vitamin B12
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 5 sitesin 2 countries
- Study dates
- Mar 2010to Aug 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania, 15213
Stanford University School of Medicine
Stanford, California, 94305
About this study
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
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.
Read the 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
- Being tested
- Pralatrexate Injection, Bexarotene Capsules, Vitamin B12, Folic Acid
- Keywords
- Relapsed, Refractory
- Medical subject headings
- Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Sezary Syndrome, Lymphoma, Primary Cutaneous Anaplastic Large Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pralatrexate InjectionDrug
Also called FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterin
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 CapsulesDrug
Also called Bexarotene, Targretin®
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 B12Dietary supplement
Also called Cyanocobalamin
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 AcidDietary supplement
Also called Vitamin B9, Folate, Folacin
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).
| Study group | Role | What they receive |
|---|---|---|
| Bexarotene (Targretin) & Pralatrexate (Folotyn) | Experimental | 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. Receives: Drug: Pralatrexate Injection; Drug: Bexarotene Capsules; Dietary Supplement: Vitamin B12; Dietary Supplement: Folic Acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT) Rate
DLT rate is the number of patients experiencing a DLT divided by number of evaluable patients and it will be summarized by dose level.
Measured: Assessed weekly through cycle 1 (weeks 1-4)
Secondary outcomes (3)
Overall Response Rate (ORR)
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.
Measured: Assessed after every 2 cycles (8 weeks) for the first 12 months, then every 4 cycles (16 weeks) until progression of disease.
Number of Patients with Treatment-related Adverse Events (AEs) and Serious AEs (SAEs)
(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
Measured: 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).
Pharmacokinetic Parameters
This was collected during the dose-finding stage of the study. PK sampling is not included in the cohort expansion.
Measured: Sampling through 24 hours post end-injection of pralatrexate in cycle 1 dose 1 (week 1) and cycle 1 dose 3 (week 3).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2010 (estimated)
- Study startMar 2010
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous T-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Acrotech Biopharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pankaj Sharma, MD, Study director, Spectrum Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01134341
- Sponsor's protocol ID
- PDX-018
- Status last verified
- Dec 2019
- First submitted
- 28 May 2010
- Last updated
- 18 Dec 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01134341
- Acronym / sponsor ID
- PDX-018
- Conditions
- Cutaneous T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome, Primary Cutaneous Anaplastic Large Cell Lymphoma
- Keywords
- Relapsed, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Acrotech Biopharma Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2010
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 2 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bexarotene (Targretin) & Pralatrexate (Folotyn) | Experimental | Drug: Pralatrexate Injection, Drug: Bexarotene Capsules, Dietary Supplement: Vitamin B12, Dietary Supplement: Folic AcidBexarotene (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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pralatrexate InjectionAlso: FOLOTYN, PDX, Pralatrexate, (RS)-10-propargyl-10-deazaaminopterinIntravenous (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 (Targretin) & Pralatrexate (Folotyn) |
| Bexarotene CapsulesAlso: Bexarotene, Targretin®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. | Drug | Bexarotene (Targretin) & Pralatrexate (Folotyn) |
| Vitamin B12Also: Cyanocobalamin1 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). | Dietary supplement | Bexarotene (Targretin) & Pralatrexate (Folotyn) |
| Folic AcidAlso: Vitamin B9, Folate, Folacin1-1.25 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). | Dietary supplement | Bexarotene (Targretin) & Pralatrexate (Folotyn) |
Primary outcome
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.
3 secondary outcomes
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.
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).
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pankaj Sharma, MD study director
Spectrum Pharmaceuticals, Inc
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pralatrexate Injection, Bexarotene Capsules and Vitamin B12 in people with Cutaneous T-cell Lymphoma and Mycosis Fungoides, run by Acrotech Biopharma Inc. at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) Rate (time frame: Assessed weekly through cycle 1 (weeks 1-4)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2019.