Clinical Trials /

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

NCT03485547

Description:

This research study is studying a drug as a possible treatment for BPDCN. The intervention involved in this study is: Venetoclax

Related Conditions:
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 18-045
  • NCT ID: NCT03485547

Conditions

  • Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

DrugSynonymsArms
VenetoclaxVenclextaVenetoclax

Purpose

This research study is studying a drug as a possible treatment for BPDCN. The intervention involved in this study is: 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.
    

Trial Arms

NameTypeDescriptionInterventions
VenetoclaxExperimentalVenetoclax 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.
  • Venetoclax

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:
Measure:Complete Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Partial Response
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • BPDCN

Last Updated

October 17, 2019