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Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma

ConditionsT-cell LymphomaCutaneous/Peripheral T-Cell LymphomaPeripheral T-cell LymphomaPeripheral T-Cell Lymphoma, Not ClassifiedPrimary Cutaneous T-cell LymphomaCutaneous T-Cell Lymphoma, UnspecifiedCutaneous T-cell LymphomaFollicular T-Cell LymphomaAngioimmunoblastic T-cell LymphomaSézary's DiseaseMycosis Fungoides
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorSciTech Development, Inc.

About this trial

This study evaluates a fenretinide phospholipid suspension for the treatment of T-cell non-Hodgkin's lymphoma (NHL).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Cutaneous T-cell lymphoma (CTCL): mycosis fungoides (MF), Sézary Syndrome (SS), or primary cutaneous CD30+ anaplastic large cell lymphoma (cALCL).

Nodal TCL: Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), or follicular T-cell lymphoma (FTCL) as defined in the 2016 revision of the WHO classification of lymphoid malignancies[98] (Appendix A).

For standard phase 1a and expanded cohort (1b): Patients must all have at least one measurable disease site using criteria provided in section 11.

Relapsed or refractory (R/R) disease, after at least 1 prior treatment regimen as per disease staging (including but not limited to oral bexarotene, interferon, any oral or IV HDAC inhibitor, any topical, oral or IV chemotherapy drugs, radiotherapy, retinoids, topical steroids, systemic steroids, phototherapy, immunomodulators, Biologics and others based on PI discretion. Refer to section 2.1 of the protocol for more details).

Disqualifiers

Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

Patients who are receiving any other investigational agents.

Patients with known or history of central nervous system (CNS) disease are excluded from this clinical trial because of their poor prognosis and because of concerns regarding toxicity attribution.

History of allergic reactions or sensitivity to retinoids or to any excipients of ST-001.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Fenretinide

    Drug

    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

Treatment groups

46 Participants
are divided into 1 treatment group
Group A: Phase 1Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Maximum Tolerated Dose (MTD)

To determine the MTD of ST-001 nanoFenretinide (12.5mg/mL) for IV infusion in patients with CTCL and other T-cell NHL.

Time frame
12 months

Secondary outcomes

1

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

The number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0 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.

Time frame
12 months
2

Number of participants with complete response (CR) or partial response (PR) to ST-001

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.

Time frame
24 months
3

Fenretinide Cp(plateau), half-life (t1/2), and calculated parameters of Clearance and Volume of Distribution

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.

Time frame
18 months
4

Activation of cytolytic T-lymphocytes (CTLs) and natural killer (NK) cells after ST-001 treatment.

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.

Time frame
24 months

Other outcomes

Sponsors and contacts

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SciTech Development, Inc.

Lead sponsor

Source ClinicalTrials.gov
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