Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT04234048|
Recruitment Status : Not yet recruiting
First Posted : January 21, 2020
Last Update Posted : January 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|T-cell Lymphoma Cutaneous/Peripheral T-Cell Lymphoma Peripheral T-cell Lymphoma Peripheral T-Cell Lymphoma, Not Classified Primary Cutaneous T-cell Lymphoma Cutaneous T-Cell Lymphoma, Unspecified Cutaneous T-cell Lymphoma Follicular T-Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Sézary's Disease Mycosis Fungoides||Drug: Fenretinide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose escalation oncology Phase 1 with extended cohort study (1b); Up to 46 patients for the whole study: up to 8 patients for accelerated phase 1a (single patient cohort) + up to 18 patients for standard phase 1a (3+3 design) + 20 patients for phase 1b at the maximum tolerated dose (MTD)|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1a/1b Trial in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma to Determine the Safety Profile, Pharmacology, and Maximum Tolerated Dose of ST-001, a Fenretinide Phospholipid Suspension (12.5 mg/mL) for Intravenous Infusion|
|Estimated Study Start Date :||July 2020|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||July 2022|
Experimental: Phase 1
Accelerated Phase 1a + Standard Phase 1a + Phase 1b
Accelerated Phase 1a
Up to 8 patients for accelerated phase 1a (single patient cohort); dose levels of ST-001 nanoFenretinide (mg/m^2/day X 5 days every 21 days):
Dose Level 1 1.25 (1 patient) Dose Level 2 2.5 (1 patient) Dose Level 3 5.0 (1 patient) Dose Level 4 10 (1 patient) Dose Level 5 20 (1 patient) Dose Level 6 40 (1 patient) Dose Level 7 80 (1 patient) Dose Level 8 160 (1 patient)
Standard Phase 1a
Up to 18 patients for standard phase 1a (3+3 design); dose level (mg/m2/day X 5 days every 21 days):
Dose Level 9 320 (3-6 patients) Dose Level 10 448 (3-6 patients) Dose Level 11 627 (3-6 patients)
20 patients for phase 1b at the maximum tolerated dose (MTD)
Accelerated Phase 1a 100% Dose escalation in 8 single-patient cohorts
Standard Phase 1a 40% Dose escalation in 3-patient cohorts X 3 cohorts
Phase 1b Dosed at MTD in 20 patients as disease-specific expanded cohort
- Maximum Tolerated Dose (MTD) [ Time Frame: 12 months ]To determine the MTD of ST-001 nanoFenretinide (12.5mg/mL) for IV infusion in patients with CTCL and other T-cell NHL.
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 12 months ]The number of participants with treatment-related adverse events as assessed by NCI CTCAE v4.0 will be determined. All patients who receive any dose of ST-001 will be evaluable for toxicity. The incidence rates of adverse events (AEs) will be tabulated by system organ class and preferred term, and by severity. All AEs with corresponding attributes will be displayed in a by-patient listing. The investigator at each site will determine the causal relationship between study medication and AEs. Subsets of AEs to be summarized include Severe Adverse Events (SAEs), suspected treatment-related AEs, and AEs that resulted in withdrawal of treatment or death.
- Number of participants with complete response (CR) or partial response (PR) to ST-001 [ Time Frame: 24 months ]Any patient who has at least one measurable disease site and has received at least on full cycle (5-day infusion) of ST-001 is eligible for response-to-treatment evaluation. The frequency and proportion of subjects with CR or PR will be calculated with a 95% Clopper Pearson confidence interval. CR + PR will constitute the overall response rate (ORR). The Global Response Scale (GRS) will be used to determine response of CTCL patients to ST-001. The GRS incorporates all components of the TNMB system (skin, lymph nodes, viscera, and blood). The International Working Group (IWG) Criteria for Response Assessment will be used to determine response in non-CTCL T-NHL patients.
- Fenretinide Cp(plateau), half-life (t1/2), and calculated parameters of Clearance and Volume of Distribution [ Time Frame: 18 months ]Pharmacokinetic (PK) evaluation of fenretinide Cp X t curves, Cp(plateau), and half-life (t1/2) as well as calculated parameters of Clearance and Volume of Distribution will be conducted at each dose level when all of its planned first cycle treatments have been completed. PK analysis will use descriptive statistics to characterize the range, median, and mean of calculated values of fenretinide clearance, volume of distribution, and distribution and elimination phase half-lives across all evaluable patients using individual patient C X t data. The relationship between dose and CpMAX and/or AUC will be examined as will their relationship to grade of toxicity.
- Activation of cytolytic T-lymphocytes (CTLs) and natural killer (NK) cells after ST-001 treatment. [ Time Frame: 24 months ]The pharmcodynamic (PD) effect of ST-001 will be evaluated in tissue biopsies taken from tumorous skin lesions of CTCL patients. CTL and NK cell activation will be measured by expression of granzyme A and B, perforin, and NKG2D using immunohistochemical staining (IHC) of tissue biopsies. In addition, CTLs and NK cell tumor infiltration will be evaluated using CD8 and CD56 IHC staining, respectively. Biomarker analysis will use each patient's baseline (pre-treatment) values as the Control value and normalize PD changes as % change from baseline. In addition, the baseline PD biomarker values across all evaluable patients will be characterized as a distribution, and the on-treatment PD responses analyzed for values that are statistical outliers from the baseline distribution of values.
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): NCT04234048
|Contact: Louis M Scarmoutzos, PhD||(617) firstname.lastname@example.org|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|Contact: Chrystal Johnston, MS 312-563-2312 email@example.com|
|Contact: Pamela A Sroka, BSN RN CCRC (312) 942-5526 firstname.lastname@example.org|
|Principal Investigator: Timothy M Kuzel, MD|
|Study Director:||Ayad Al-Katib, MD||SciTech Development, LLC|
|Principal Investigator:||Timothy M Kuzel, MD||Rush University Medical Center|