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

NCT04234048 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ST-001-010
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

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

Keywords

Lymphoma; CTCL; Sézary syndrome; mycosis fungoides; PTCL; AITL; cALCL

Outcome Measures

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.

  12 months

Secondary Outcomes (4)

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

  12 months

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

  24 months

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

  18 months

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

  24 months

Study Arms (1)

Phase 1

EXPERIMENTAL

Accelerated Phase 1a + Standard Phase 1a + Phase 1b Accelerated Phase 1a Up to 9 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) Dose Level 9 320 (1 patient) Standard Phase 1a Up to 15 patients for standard phase 1a (3+3 design); dose level (mg/m2/day X 5 days every 21 days): Dose Level 10 640 (3-6 patients) Dose Level 11 896 (3-6 patients) Dose Level 12 1,254 (3-6 patients) Dose Level 13 1,756 (3-6 patients) Phase 1b 20 patients for phase 1b at the maximum tolerated dose (MTD)

Drug: Fenretinide

Interventions

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

Also known as: nanoFenretinide, ST-001, 4-HPR, N-(4-hydroxyphenyl)retinamide, N-(4-hydroxyphenyl)-all-trans-retinamide

Phase 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must have histologically or cytologically confirmed diagnosis of the following specific types of T-cell lymphomas (TCL):
• 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).
• Refractory disease is defined as lack of objective response (i.e., partial or complete response) to most recent therapy.
• Relapsed disease is defined as recurrent disease after prior therapy that does not qualify as refractory disease.
• Other systemic treatments not specified may be allowed based on PI judgement in consultation with the Sponsor.
• For primary cutaneous lymphomas, stage IB, II, III and IV according to the TNMB system (Appendix C) are eligible. For primary nodal lymphomas, patients with stages II-IV according to the Ann Arbor staging system are eligible.
• Minimum of 4 weeks must have elapsed since last systemic treatment or radiation therapy treatment (or 6 weeks for any nitrosourea-containing regimens), and patients must have recovered from all toxicity of last treatment. If the PI assesses that it is in the best interest of the patient to have a shorter washout period, they may submit a written request to the sponsor and can enroll the patient after written approval has been received.
• Age ≥18 years. Both genders are included. However, women of childbearing potential must have a negative B-HCG serum pregnancy test (see Section 10 Study Calendar, Pre-Study, footnote b) and agree to use effective contraceptive methods for the duration of the study. A urine pregnancy test is required just prior to the first dosing session of every treatment cycle.
• ECOG performance status 0-1 (Karnofsky ≥60%, see Appendix B).
• Life expectancy greater than 6 months.
• Patients must have normal organ and marrow function as defined below:
• Leukocytes ≥ 3,000/μL

You may not qualify if:

• 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.
• Concomitant drug administration.
• Patients who require concurrent treatment with drugs that are strong CYP3A inducers are excluded from the trial. Patients who have been treated previously with strong CYP3A inducers may enroll in the trial and receive their first dose of ST-001 only after four weeks have elapsed since the last dose of the CYP3A inducer. Strong inducers of human CYP3A include barbiturates, bosentan, carbamazepine, efavirenz, enzalutamide, etravirine, systemic glucocorticoids, mitotane, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, troglitazone as well as the OTC herbal product St John's Wort (https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#table2-3; http://www.mayomedicallaboratories.com/it-mmfiles/Cytochrome\_P450\_3A4\_and\_3A5\_Known\_Drug\_Interaction\_Chart.pdf; http://oncologypro.esmo.org/content/download/66542/1203090/file/CYP3A-inhibitors-inducers-DDI.pdf)
• Patients who require concurrent treatment with drugs that are strong to moderate CYP3A inhibitors are excluded from the trial, and patients who have been treated previously with strong CYP3A inhibitors may enroll in the trial and receive their first dose of ST-001 only after four weeks have elapsed since the last dose of the CYP3A inhibitor. This group of inhibitors includes certain antivirals (boceprevir, danoprevir, paritaprevir; elvitegravir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, telaprevir, tipranavir; ombitasvir, dasabuvir), macrolide antibiotics (e.g., clarithromycin, erythromycin, telithromycin, troleandomycin) and ciprofloxacin, antifungals (e.g., clotrimazole, fluconazole, ketoconazole, itraconazole, nefazodone, posaconazole, voriconazole), aprepitant, cimetidine, cobicistat, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone, idelalisib, luvoxamine, imatinib, tofisopam, suboxone and verapamil as well as dietary grapefruit juice and grapefruit (https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#table2-3; http://www.mayomedicallaboratories.com/it-mmfiles/Cytochrome\_P450\_3A4\_and\_3A5\_Known\_Drug\_Interaction\_Chart.pdf; http://oncologypro.esmo.org/content/download/66542/1203090/file/CYP3A-inhibitors-inducers-DDI.pdf)
• If patients being treated with ST-001 require the use of drugs that are either strong inducers of CYP3A or strong to moderate inhibitors of CYP3A to treat a medical condition, all treatment with ST-001 should be discontinued immediately and no further treatment with ST-001 will be allowed.
• Use of acetaminophen, cephalosporins and other known hepatotoxic agents is allowed with caution and close monitoring, due to known or potential interaction with ST-001 and potential increased risk of hepatotoxicity\[52\]. Patients who require replacement therapy with oral steroids should be allowed to continue the treatment if treatment with stable dose has been initiated more than 2 weeks prior to beginning ST-001 infusion. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated list such as http://medicine.iupui.edu/clinpharm/ddis/. Medical reference texts such as the Physicians' Desk Reference may also provide this information.
• As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Physician investigators should consult the websites listed above for the most current information regarding drug interactions via CYP3A isozymes.
• Use of vitamin A supplements is prohibited. Standard multivitamin doses are allowed.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (NY heart classification III/IV), unstable angina pectoris, cardiac arrhythmia, QTc interval \>450 milliseconds on baseline triplicate ECG, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because ST-001is a retinoid agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ST-001, breastfeeding should be discontinued if the mother is treated with ST-001.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ST-001. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients with any active hepatitis infections.

Sponsors & Collaborators

• SciTech Development, Inc.: lead

Study Sites (10)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

City of Hope Medical Foundation

Duarte, California, 91010, United States

RECRUITING

University of Southern California

Los Angeles, California, 90007, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Northwestern University, Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute Wayne State University

Detroit, Michigan, 48201, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

University of Pittsburgh Medical Center (UPMC)

Pittsburgh, Pennsylvania, 15219, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Immunoblastic Lymphadenopathy; Sezary Syndrome; Mycosis Fungoides; Lymphoma

Interventions

Fenretinide; MAC-ST-001

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors

Study Officials

• Ali Moiin, MD

  SciTech Development, Inc.

  STUDY DIRECTOR

• Oleg E Akilov, MD, PhD

  University of Pittsburgh Medical Center (UPMC)

  PRINCIPAL INVESTIGATOR

• Ann F Mohrbacher, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

• Barbara Pro, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Dipenkumar Modi, MD

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

• Auris O Huen, MD, PharmD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Ryan A Wilcox, MD, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Brad Haverkos, M.D.

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Christiane Querfeld, M.D., Ph.D.

  City of Hope Medical Foundation

  PRINCIPAL INVESTIGATOR

• Aaron R Mangold, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Jonathan Moreira, M.D.

  Northwestern University, Robert H. Lurie Comprehensive Cancer Center

  STUDY DIRECTOR

Central Study Contacts

Louis M Scarmoutzos, PhD

CONTACT

(617) 283-2182; lou@scitechdevelopment.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 21, 2020
• Study Start: December 18, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)