Dasatinib In Waldenström Macroglobulinemia

NCT04115059 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 19-305
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is Phase I pilot, single center study designed to explore the safety of Dasatinib in symptomatic Waldenström Macroglobulinemia participants who are progressing on ibrutinib therapy with BTK Cys481 or PLCG2 mutations

Conditions

Waldenstrom Macroglobulinemia; DASATINIB

Keywords

Waldenstrom Macroglobulinemia; DASATINIB

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least One Treatment-Emergent Adverse Event

  Count of participants who experience a treatment-emergent adverse event

  2 years

Secondary Outcomes (10)

• Overall Response Rate

  2 years

• Complete Response Rate

  2 years

• Very Good Partial Response Rate

  2 years

• Partial Response Rate

  2 years

• Minimal Response Rate

  2 years

Study Arms (1)

Dasatinib

EXPERIMENTAL

\-- After the screening procedures confirm participation in the research study: The participant will be given a study drug-dosing calendar for each treatment cycle. Dasatinib: Oral Study Drug(s): * Each study treatment cycle lasts 4 weeks during which time you will be taking the study drug one time per day. * This will continue for up to 24 cycles.

Drug: Dasatinib

Interventions

Dasatinib DRUG

Oral, daily, dosing per protocol, once a day for cycle

Also known as: Sprycel

Dasatinib

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate. Screening evaluations including consent, physical exam, and laboratory assessments will be done within 30 days prior to Cycle 1 Day 1. Bone marrow biopsy \& aspirate, and CT C/A/P will be done within 90 days prior to Cycle 1 Day 1.
• Clinicopathological diagnosis of Waldenstrom's Macroglobulinemia
• Known tumor expression of mutated MYD88 performed by a CLIA certified laboratory.
• Participants must have a BTKCys481 and/or PLCγ2 mutation. Genomic alterations must be confirmed via sequencing performed at NeoGenomics Laboratories
• At least one previous therapy, with ibrutinib as the most recent treatment. Participants may remain on ibrutinib therapy during screening. A 1 day washout before starting dasatinib is required.
• Documented disease progression on last regimen (ibrutinib) per the Sixth International Workshop on WM. One or more of the following:
• % increase in serum IgM level with at least 500 mg/dL absolute increase from nadir with re-confirmation
• Progression of clinically significant disease related symptoms
• Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on WM \[26\]. One or more of the following:
• Constitutional symptoms
• Progressive or symptomatic lymphadenopathy or splenomegaly
• Hemoglobin \<10 g/dL
• Platelet count \<100 k/uL
• Symptomatic peripheral neuropathy
• Systemic amyloidosis

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
• Lactating or pregnant women.
• Participants who are receiving any other investigational agents.
• Prior therapy with BCR-ABL inhibitors.
• Known CNS lymphoma.
• Symptomatic hyperviscosity requiring urgent therapy.
• Human Immunodeficiency Virus (HIV), active infection with Hepatitis B Virus (HBV), and/or Hepatitis C Virus (HCV).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, pleural or pericardial effusion, unstable angina pectoris, cardiac arrhythmia, QT Prolongation, or psychiatric illness/social situations that would limit compliance with study requirements.
• Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
• History clinically significant ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes
• Known history of alcohol or drug abuse
• On any active therapy for other malignancies with the exception of topical therapies for basal cell or squamous cell cancers of the skin.
• History of non-compliance to medical regimens.
• Treatment with strong CYP3A4/5 inhibitors or inducers
• Participants who are taking St. Johns Wort. Must discontinue at least 5 days before starting dasatinib.

Sponsors & Collaborators

• Jorge J. Castillo, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Castillo JJ, Sarosiek S, Flynn CA, Leventoff C, Little M, White T, Meid K, Treon SP. A pilot study on dasatinib in patients with Waldenstrom macroglobulinemia progressing on ibrutinib. EJHaem. 2022 Jun 7;3(3):927-929. doi: 10.1002/jha2.493. eCollection 2022 Aug.

  PMID: 36051045 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Dasatinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Jorge Castillo
• Organization: Dana-Farber Cancer Institute

jorgej_castillo@dfci.harvard.edu

617-632-2681

Study Officials

• Jorge Castillo, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 3, 2019
• Study Start: November 4, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 21, 2024
• Results First Posted: March 21, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)