A Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL)

NCT04171791 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2000022803
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.

Conditions

CTCL

Outcome Measures

Primary Outcomes (6)

• Body Temperature

  Safety and tolerability endpoints will be evaluated on the basis of body temperature.

  Up to 32 weeks

• Blood Pressure- Diastolic

  Safety and tolerability endpoints will be evaluated on the basis of blood pressure.

  Up to 32 weeks

• Blood Pressure- Systolic

  Safety and tolerability endpoints will be evaluated on the basis of blood pressure.

  Up to 32 weeks

• Pulse Rate

  Safety and tolerability endpoints will be evaluated on the basis of pulse rate.

  Up to 32 weeks

• Respiratory Rate

  Safety and tolerability endpoints will be evaluated on the basis of respiratory rate.

  Up to 32 weeks

• Adverse Events

  Adverse events will be used to measure the study defined outcome:Toxicity. Toxicity (as adverse events) will measured according to the NCI CTCAE (v5.0) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of venetoclax and up to four weeks after last dose (Termination visit).

  Up to 32 weeks

Secondary Outcomes (3)

• Skin Clinical Response

  Up to 32 weeks

• Duration of Response

  Up to 32 weeks

• Relapse Free and Progression Free Survival

  Up to 32 weeks

Study Arms (1)

ABT-199 (Venetoclax)

EXPERIMENTAL

Patients with Cutaneous T Cell Lymphoma (CTCL) will receive ABT-199 (Venetoclax).

Drug: ABT-199 (venetoclax)

Interventions

ABT-199 (venetoclax) DRUG

Eligible patients will be enrolled into the study and receive venetoclax daily per the US FDA package insert guidelines of venetoclax, with dose escalation up to 400 mg. To minimize the risk of tumor lysis syndrome (TLS), and following the package insert directions for dose escalation over 5 weeks, the initial dose is 20 mg daily, and may be progressively increased as tolerated to 400 mg by week 5.

ABT-199 (Venetoclax)

Eligibility Criteria

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

You may qualify if:

• Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides), stage IB-IV (hereafter referred to as advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable.
• All subjects must have shown disease refractory to one or more standard systemic therapy (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or total skin electron beam therapy over 3 months, or have demonstrated relapsed or progressive disease at any time while receiving one or more of therapies.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Adequate bone marrow function: WBC \> 2000/µL; platelet count \> 75,000/mm3; Neutrophil count \> 1000/µL, without use of colony stimulating factors (CSF).
• Required washout period for prior therapies
• Spot Skin Radiation Therapy (≤10% skin surface): 4 weeks
• Systemic therapy: 4 weeks, or until recovered from toxicities
• Women of child-bearing potential must have negative serum pregnancy test and use accepted highly effective methods of birth control throughout the study and for 90 days after dosing and must agree to use effective contraception, such as hormonal birth control (must be at least 3 years without complications), intrauterine devices, double barrier method (condom plus spermicide or diaphragm), or abstain from sexual intercourse.
• Male patients must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study and for 90 days after dosing.
• Adequate hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), AST ≤3.0 x ULN, ALT ≤ 3.0 x ULN
• Adequate renal function: creatinine clearance ≥ 50 mL/min
• Ability to comply with the treatment schedule

You may not qualify if:

• Extracutaneous disease except blood, bone marrow and lymph nodes.
• Concomitant use of any systemic anti-cancer therapy or immune modifier.
• Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of study drug administration.
• Patients with biopsy confirmed transformed MF.
• Prior allogeneic hematopoietic cell transplant.
• Any ongoing infection requiring antibiotics within 2 weeks prior to the start of the study drug, except for antibiotics (e.g. cephalexin) prescribed superficial skin infection.
• Known history of human immunodeficiency virus (HIV), hepatitis B or C.
• History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA \<1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years.
• Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study including, but not limited to, the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions.
• Major surgery within 8 weeks of enrollment.
• Medically significant cardiac event or unstable cardiovascular function defined as:
• Symptomatic ischemia, unstable angina pectoris
• Uncontrolled clinically significant cardiac arrhythmia
• Symptomatic heart failure NYHA Class ≥ 3
• Myocardial infarction or cardiac surgery within 6 months prior to enrollment

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale New Haven Hospital / Smilow Cancer Center

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Interventions

venetoclax

Study Officials

• Michael Girardi, MD, FAAD

  Professor of Dermatology Yale University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: November 21, 2019
• Study Start: January 15, 2020
• Primary Completion: February 10, 2021
• Study Completion: June 22, 2021
• Last Updated: June 25, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)