Clinical Trials /

Dasatinib In Waldenström Macroglobulinemia

NCT04115059

Description:

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

Related Conditions:
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dasatinib In Waldenström Macroglobulinemia
  • Official Title: Dasatinib in Patients With Waldenström Macroglobulinemia (WM) Progressing on Ibrutinib

Clinical Trial IDs

  • ORG STUDY ID: 19-305
  • NCT ID: NCT04115059

Conditions

  • Waldenstrom Macroglobulinemia
  • DASATINIB

Interventions

DrugSynonymsArms
DasatinibSprycelDasatinib

Purpose

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

Detailed Description

      This research study is a Pilot Study, which is the first time investigators are examining
      this drug in patients with Waldenström Macroglobulinemia who have progressed on ibrutinib.

      Patients who fulfill eligibility criteria will be entered into the trial to receive Dasatinib

      After the screening procedures confirm participation in the research study:

      The participant will be given a study drug-dosing calendar for each treatment cycle. In this
      research study, the investigators are planning to give Dasatinib, which is a targeted therapy
      intended to treat cancer by binding to the target protein called BTK.

        -  BTK is believed to be an important target for treatment of patients with specific gene
           mutations. Some patients who have disease progression after taking ibrutinib have these
           gene mutations.

        -  Making treatment decisions based on genetic testing is investigational, and the FDA has
           not approved this genetic testing.

      The U.S. Food and Drug Administration (FDA) has not approved Dasatinib for Waldenström
      Macroglobulinemia but it has been approved for other uses.

      Dasatinib is produced by Bristol-Myers Squibb.
    

Trial Arms

NameTypeDescriptionInterventions
DasatinibExperimental-- 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.
  • Dasatinib

Eligibility Criteria

        Inclusion Criteria:

          -  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:

          -  25% 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

               -  Renal insufficiency

               -  Symptomatic cryoglobulinemia

          -  Age 18 years or older

          -  Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a
             minimum serum IgM level of > 2 times the upper limit normal.

          -  ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)

          -  Women of childbearing potential: Females of childbearing potential (FCBP) must agree
             to use two reliable forms of contraception simultaneously or have or will have
             complete abstinence from heterosexual intercourse during the following time periods
             related to this study: 1) while participating in the study; and 2) for at least 28
             days after discontinuation from the study. FCBP must be referred to a qualified
             provider of contraceptive methods if needed.

          -  Men must agree to use a latex condom during sexual contact with a female of
             childbearing potential (FCBP) even if they have had a successful vasectomy.

          -  Participants must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count ≥500/ uL (Growth factor not permitted)

               -  Platelets ≥50,000/ uL (Platelet transfusion not permitted)

               -  Hemoglobin ≥ 7 g/dL (RBC transfusion permitted)

               -  Total bilirubin ≤ 2 mg/dL

               -  Potassium ≥ LLN

               -  Magnesium ≥ LLN

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               -  Estimated GFR ≥ 30 ml/min

          -  Able to swallow pills.

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  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.

          -  Treatment with H2 Antagonists and proton pump inhibitors
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate the toxicity profile of dasatinib in WM patients who progressed on ibrutinib with BTK or PLCG2 mutations.
Time Frame:2 years
Safety Issue:
Description:Number and type of toxicities experienced by patients related to dasatinib.

Secondary Outcome Measures

Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with MR, PR, VGPR, or CR to therapy.
Measure:Complete Response Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with CR
Measure:Very good partial response rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with VGPR to therapy. (VGPR is >90% reduction in serum IgM from baseline)
Measure:Partial Response Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with PR to therapy. (PR is 50-89% reduction in serum IgM from baseline)
Measure:Minimal Response Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with Minor Responses to therapy. (MR is 25-49% reduction in serum IgM from baseline)
Measure:Stable Disease Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with Stable disease to therapy. (SD is <25% reduction in serum IgM from baseline).
Measure:Progressive Disease Rate
Time Frame:2 years
Safety Issue:
Description:Proportion of patients with a best response of PD to therapy. (PD is >25% increase in serum IgM from baseline).
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:Kaplan Meier methodology
Measure:Time to Next Therapy (TTNT)
Time Frame:2 years
Safety Issue:
Description:Kaplan Meier
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Kaplan Meier

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jorge J. Castillo, MD

Trial Keywords

  • Waldenstrom Macroglobulinemia
  • DASATINIB

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