Cutaneous T-Cell Lymphoma Clinical Trial
Official title:
Phase I/II Study of Oral Bexarotene in Combination With Photopheresis for Treatment of Cutaneous T-Cell Lymphoma
This is a pilot study of the safety and tolerability of photopheresis in combination with increasing doses of oral bexarotene in patients with cutaneous T-cell lymphoma.Our hypotheses are that the combination of bexarotene with photopheresis is safe and that bexarotene will enhance immune response in the setting of extracorporeal photopheresis in the treatment of cutaneous T-cell lymphoma (CTCL), resulting in a shorter time to clinical response.
Photopheresis is FDA-approved as a device in the treatment of patients with cutaneous T-cell
lymphoma. Using treatment schedules of once monthly treatment, with each treatment
consisting of two consecutive days of photopheresis, initial response rates of 20-60% have
been reported. However, in publications, for those who attained a complete response, median
time to response was 11 months (range 5 to 14 months). Response has been shown to correlate
with intact immune function in patients with normal CD8+ cell prior to therapy. The
mechanism of activity of photopheresis in cutaneous T-cell lymphoma while not fully
understood involves apoptosis of malignant tumor cells. Modifications in the original
scheduling of photopheresis, with shorter cycles of 2 or 3 weeks, have met with success.
Several centers have been using an accelerated delivery schedule of treatments, treating
patients every 2 weeks.
Bexarotene was FDA approved for patients with CTCL. It is an RXR selective retinoid.
Retinoids can serve as physiologic rather than cytotoxic drugs to arrest or reverse the
process of carcinogenesis. There is a growing body of evidence that supports a role for
retinoids in the induction of apoptosis. In the two, completed Phase II-III studies that
formed the basis of approval (approved dose is 300mg/m2/day) of bexarotene capsules, 193
patients with previously treated CTCL were administered bexarotene capsules. Response rates
were in the order of 50% for the 300mg/2/day, however, 79% of patients had hyperlipidemia.
This study will therefore primarily examine the safety and tolerability of using increasing
doses of bexarotene in combination with photopheresis. As a secondary endpoint, we will
attempt to establish whether bexarotene can upregulate the immune response and therefore
potentially enhance the response rates to photopheresis in patients with CTCL.
Six cohorts of patients will be treated:
Dose level cohorts enrollment will be sequential with centralized dose assignment at Boston
Medical Center
To establish safety, a 30 day pause will occur between cohorts. During the 30 day waiting
period, additional patients will be able to enter the open cohort, provided that there is no
grade 3 or 4 toxicity in the 3 patients already entered into the cohort. Once the 30 day
period has ended, new patients will be able to enter the next cohort.
Cohort 1 (3 patients): Bexarotene will be given at the dose of 75mg po per day with food for
7 days prior to beginning photopheresis(Day –6 to 0, day 1 being the day when photopheresis
begins on first day of cycle 1). Photopheresis will be performed on 2 consecutive days the
first 2 days of each 21 day cycle. Bexarotene will be given concurrently with photopheresis
for 4 cycles. The duration of the study is 3 months with premature discontinuation for
toxicity at the discretion of the investigator, or progressive disease.
Cohort 2 (3 patients): Bexarotene will be given at the dose of 150 mg po per day with food
for 7 days prior to beginning photopheresis (Day –6 to 0, day 1 being the day when
photopheresis begins on first day of cycle 1). Photopheresis will be performed on 2
consecutive days the first 2 days of each 21 day cycle. Bexarotene will be given
concurrently with photopheresis for 4 cycles. The duration of the study is 3 months with
premature discontinuation for toxicity at the discretion of the investigator, or progressive
disease.
Cohort 3 (3 patients): Bexarotene will be given at the dose of 225 mg po per day with food
for 7 days prior to beginning photopheresis (Day –6 to 0, day 1 being the day when
photopheresis begins on first day of cycle 1). Photopheresis will be performed on 2
consecutive days the first 2 days of each 21 day cycle. Bexarotene will be given
concurrently with photopheresis for 4 cycles. The duration of the study is 3 months with
premature discontinuation for toxicity at the discretion of the investigator, or progressive
disease.
Cohort 4 (3 patients): Bexarotene will be given at the dose of 300 mg po per day with food
for 7 days prior to beginning photopheresis (Day –6 to 0, day 1 being the day when
photopheresis begins on first day of cycle 1). Photopheresis will be performed on 2
consecutive days the first 2 days of each 21 day cycle. Bexarotene will be given
concurrently with photopheresis for 4 cycles. The duration of the study is 3 months with
premature discontinuation for toxicity at the discretion of the investigator, or progressive
disease.
Cohort 5 (3 patients): Bexarotene will be given at the dose of 375 mg po per day with food
for 7 days prior to beginning photopheresis (Day –6 to 0, day 1 being the day when
photopheresis begins on first day of cycle 1). Photopheresis will be performed on 2
consecutive days the first 2 days of each 21 day cycle. Bexarotene will be given
concurrently with photopheresis for 4 cycles. The duration of the study is 3 months with
premature discontinuation for toxicity at the discretion of the investigator, or progressive
disease.
Cohort 6 (3 patients): Bexarotene will be given at the dose of 450 mg po per day with food
for 7 days prior to beginning photopheresis (Day –6 to 0, day 1 being the day when
photopheresis begins on first day of cycle 1). Photopheresis will be performed on 2
consecutive days the first 2 days of each 21 day cycle. Bexarotene will be given
concurrently with photopheresis for 4 cycles. The duration of the study is 3 months with
premature discontinuation for toxicity at the discretion of the investigator, or progressive
disease.
Toxicity will be assessed using the National Cancer Institute common Toxicity Criteria at
the beginning of each 21 day cycle. Assessments will be every 3 weeks and at the final
follow-up visit.
All patients will undergo a skin biopsy from lesional skin prior to entry to confirm active
disease. A portion of the biopsy will be used for immunohistochemical studies to identify
populations of activated lymphocytes in the skin and to identify apoptotic markers (TUNNEL
METHOD). A skin biopsy will be subsequently obtained after 7 days of bexarotene, and at the
end of the study. A portion of each skin biopsy will be used for immunohistochemical studies
to identify populations of activated lymphocytes in the skin (TGF-B and Fas on malignant T
cells) and to identify apoptotic markers (TUNNEL method)
All patients will undergo baseline studies of immune function, including a FACS analysis of
circulating lymphocyte populations to identify activation antigens on T-lymphocytes, as well
as in vitro assays of T-cell function such as proliferation assays and cytokine production
by cultured T-cells. These studies will be repeated after the second and fourth. For these
assays, one green top tube will be drawn on day 1 before photopheresis and on day 2 at the
completion of therapy. One serum tube (one red top) will be drawn on days 1 and 2 and serum
will be stored at -20° until the assays are performed.
In summary, the following research skin biopsies and labs will be obtained:
Baseline (Day –6): one green top and one red top Baseline (Day –6): skin biopsy from
lesional skin
Day 1 of cycle 1: skin biopsy from lesional skin
Cycles 2 and 4: Day 1: one green top and one red top Day 2 one green top and one red top
End of cycle 4: skin biopsy from lesional skin
In addition to the following evaluations, the BASELINE visit will include a history with
patient demographic. At the baseline, tri-weekly, and final visits, the following
information will be collected:
- Patient weight.
- Serum chemistries, including LDH, LFTS, albumin, uric acid, Ca, Phos, Mg, Cholesterol,
Triglycerides, Thyroid function (T4, TSH)
- CBC differential, Sezary count if applicable
- ECOG score.
- Skin assessment (previously published weighted skin score) and a description of other
symptoms attributed to CTCL, and at the final visit, an overall assessment
- Names and doses of all concomitant medications
- Quality of Life assessment (Skindex-29 and FACT-G)
The investigator will also evaluate patient’s response by organ system involvement, with an
overall assessment, as follows:
- Complete Response (CR): Resolution of all manifestations of CTCL lasting one month.
- Partial Response (PR): A 50% improvement of the sum total of all disease (CTCL) lasting
one month.
- No Change (NC): Failure to meet criteria for either response or progressive disease.
- Progression: a 25% or more progression of existing disease or the appearance of any new
disease (disease worsening).
- Flare: After an initial response (either CR or PR), an increase in the manifestation of
CTCL requiring additional treatment.
;
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT00341939 -
Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
|
||
Completed |
NCT00038025 -
A Study Of Deoxycoformycin(DCF)/Pentostatin In Lymphoid Malignancies
|
Phase 2 | |
Not yet recruiting |
NCT02881749 -
Low Dose Total Skin Electron Beam Treatment (TSEBT) Followed by Maintenance Valchlor for Patients With Mycosis Fungoides
|
Phase 2 | |
Completed |
NCT00744991 -
A Study for Participants With Relapsed Cutaneous T-Cell Lymphoma
|
Phase 2 | |
Completed |
NCT00099593 -
Immunization Against Tumor Cells in Sezary Syndrome
|
Phase 2 | |
Completed |
NCT02593045 -
Study of IPH4102 in Patients With Relapsed/Refractory Cutaneous T-cell Lymphomas (CTCL)
|
Phase 1 | |
Recruiting |
NCT00779896 -
Tazarotene 0.1% Cream For the Treatment of Cutaneous T-Cell Lymphoma: A Prospective Study
|
Phase 1/Phase 2 | |
Recruiting |
NCT00177268 -
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
|
||
Withdrawn |
NCT00969085 -
Trial of Curcumin in Cutaneous T-cell Lymphoma Patients
|
Phase 2 | |
Completed |
NCT01728805 -
Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL
|
Phase 3 | |
Completed |
NCT00412997 -
LBH589 in Adult Patients With Advanced Solid Tumors or Cutaneous T-cell Lymphoma
|
Phase 1 | |
Completed |
NCT00254332 -
Effect of Denileukin Diftitox on Immune System in CTCL Patients
|
N/A | |
Recruiting |
NCT04296786 -
Sintilimab Plus Chidamide in the Treatment of Relapsed and Refractory Cutaneous T-cell Lymphoma: a Multicenter Phase II Study
|
Phase 2 | |
Recruiting |
NCT06285370 -
A Study to Evaluate the Efficacy and Safety of KW-0761 in Chinese Subjects With Mycosis Fungoides or Sézary Syndrome Previously Treated With Systemic Therapy
|
Phase 4 | |
Completed |
NCT00071084 -
Clinical Trial of HuMax-CD4, a New Drug to Treat Advanced Stage T-Cell Lymphoma in the Skin.
|
Phase 2 | |
Completed |
NCT00896493 -
Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma
|
Phase 2 | |
Terminated |
NCT00699296 -
Study of Oral LBH589 in Patients With Cutaneous T-cell Lymphoma and Adult T-cell Leukemia/Lymphoma
|
Phase 2 | |
Completed |
NCT02676778 -
Study of E7777 in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma and Cutaneous T-cell Lymphoma
|
Phase 2 | |
Terminated |
NCT02061449 -
Poly ICLC, Radiation, and Romidepsin for Advanced Cutaneous T Cell Lymphoma
|
Phase 1 | |
Completed |
NCT01134341 -
Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma
|
Phase 1 |