Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Phase 1 Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

This research study is studying a drug as a possible treatment for BPDCN.

The intervention involved in this study is: Venetoclax

Study Overview

• Status: Active, not recruiting
• Conditions: Blastic Plasmacytoid Dendritic Cell Neoplasm
• Intervention / Treatment: Drug: Venetoclax

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the safest dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved venetoclax for this specific disease but it has been approved for other uses.

Based on laboratory data where it was found that BPDCN cells die after treatment with Venetoclax, the investigators believe that this drug will be effective in treating patients with BPDCN.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) per 2016 WHO criteria
• Age > 18 years
• In Stage 1 (modified 3+3): BPDCN relapsed after or refractory to at least one prior treatment regimen (hydroxyurea is not considered a prior treatment regimen)

• In Stage 2 (expansion):

  • (A) BPDCN relapsed after or refractory to at least one prior treatment regimen (hydroxyurea is not considered a prior treatment regimen)

    ---OR

  • (B) Treatment-naïve BPDCN, and age > 75 years; or treatment-naïve BPDCN, and age > 18 years and who decline intensive induction chemotherapy or who are unfit due to co-morbidity or other factors (see APPENDIX A for unfitness definitions)
• ECOG performance status 0, 1, or 2

• Adequate organ function as defined by:

  • Serum creatinine < 1.5x ULN
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5x ULN
  • Total bilirubin < 1.5x ULN (if total bilirubin is > 1.5x but < 3x ULN, and thought to be elevated due to Gilbert's disease or the patient's BPDCN, the subject may be eligible but must discuss with the PI)
• Ability to understand and the willingness to sign a written informed consent document.
• Able to adhere to study visit schedule and other protocol requirements including follow-up for survival assessment
• Women of child-bearing potential and men enrolled on this protocol must agree to use adequate contraception for the duration of study participation and for 2 months after completion venetoclax administration.

Exclusion Criteria:

• Prior treatment with venetoclax
• Received treatment with chemotherapy, radiation, or biologic cancer therapy within 14 days of first protocol treatment. Prior and concurrent hydroxyurea is permitted during the first cycle.
• Hematopoietic stem cell transplantation (HSCT) within 60 days of first protocol treatment, or receipt of immunosuppressive therapy for graft-versus-host disease treatment or prophylaxis within 14 days of first protocol treatment, or active graft-versus-host-disease
• Known active CNS involvement by BPDCN
• Known positive status for HIV infection; known active hepatitis B or hepatitis C infection
• Clinically significant cardiopulmonary disease including uncontrolled or NYHA class 3 or 4 congestive heart failure, uncontrolled angina, uncontrolled hypertension, uncontrolled arrhythmia, myocardial infarction or stroke within 6 months of first protocol treatment
• Patients with known active advanced malignant solid tumors are excluded (except for basal or squamous skin cancers, or carcinomas in situ). Patients with additional hematologic malignancies that require treatment are excluded.
• Patients with gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the developing fetus with venetoclax (negative urine or serum pregnancy test required within 14 days of Cycle 1, Day 1). Because nursing infants have unknown potential for adverse events secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with venetoclax.
• Infection is a common feature of BPDCN and acute leukemias. Patients with active infection are permitted to enroll provided that the infection is controlled (patients on IV or PO antibiotics are allowed). Patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control.

• Subject has received the following within 7 days prior to the initiation of study treatment:

  • Strong and moderate CYP3A inducers
  • Strong and moderate CYP3A inhibitors
• Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to the initiation of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax; Venetoclax is administered on a daily basis orally.; The investigators will use a modified 3+3 with a de-escalation dose level design to establish the appropriate and tolerable dose of venetoclax.	Drug: Venetoclax; VENCLEXTA targets BCL-2 in order to help restore the process of apoptosis. Through apoptosis, your body allows cancer cells and normal cells to self-destruct; Other Names: Venclexta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose Limiting Toxicity	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	2 years
Progression free survival	2 years
Overall Response Rate	2 years
Complete Response	2 years
Partial Response	2 years

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: AbbVie
• Investigators: Principal Investigator: Andrew Lane, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Wang SY, Thomassen K, Kurch L, Opitz S, Franke GN, Bach E, Platzbecker U, Kayser S. Combination of Tagraxofusp and Azacitidine Is an Effective Option for Relapsed Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem-Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Jul;21(7):e579-e582. doi: 10.1016/j.clml.2021.02.008. Epub 2021 Mar 2. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2018
• Primary Completion (Estimated): January 19, 2025
• Study Completion (Estimated): January 19, 2025

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Blastic Plasmacytoid Dendritic Cell Neoplasm; BPDCN
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: 18-045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No