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

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ClinicalTrials.gov Identifier: NCT03485547
Recruitment Status : Recruiting
First Posted : April 2, 2018
Last Update Posted : October 15, 2018
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Andrew Lane, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE March 27, 2018
First Posted Date  ICMJE April 2, 2018
Last Update Posted Date October 15, 2018
Actual Study Start Date  ICMJE August 23, 2018
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 30, 2018)
Dose Limiting Toxicity [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03485547 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2018)
  • Overall Response Rate [ Time Frame: 2 years ]
  • Complete Response [ Time Frame: 2 years ]
  • Partial Response [ Time Frame: 2 years ]
  • Overall Survival [ Time Frame: 2 years ]
  • Progression free survival [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Official Title  ICMJE Phase 1 Study of Venetoclax, a BCL2 Antagonist, for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Blastic Plasmacytoid Dendritic Cell Neoplasm
Intervention  ICMJE 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 Name: Venclexta
Study Arms  ICMJE 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.
Intervention: Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 30, 2018)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2025
Estimated Primary Completion Date April 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeremy M Stewart 617-582-8063 JeremyM_Stewart@dfci.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03485547
Other Study ID Numbers  ICMJE 18-045
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Andrew Lane, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Andrew Lane, MD Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP