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Waldenstrom MacroglobulinemiaPhase 1NCT04115059

Dasatinib In Waldenström Macroglobulinemia

A Phase 1 study testing Dasatinib in people with Waldenstrom Macroglobulinemia and DASATINIB, run by Jorge J. Castillo, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia, DASATINIB
What is being tested?
Dasatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
4 Nov 2019to 31 Dec 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Dasatinib in Patients With Waldenström Macroglobulinemia (WM) Progressing on Ibrutinib

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

Read the 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.

Being tested
Dasatinib
Keywords
Waldenstrom Macroglobulinemia, DASATINIB
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DasatinibDrug

    Also called Sprycel

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

Study groups in NCT04115059
Study groupRoleWhat they receive
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.
Receives: Drug: Dasatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Count of participants who experience a treatment-emergent adverse event

    Measured: 2 years

Secondary outcomes (10)

  1. Overall Response Rate

    Percentage of patients with an Overall Response. Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 2 years

  2. Complete Response Rate

    Percentage of patients with Complete Response (CR). Complete Response requires resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, and resolution of any adenopathy or splenomegaly.

    Measured: 2 years

  3. Very Good Partial Response Rate

    Percentage of patients with very good partial response (VGPR) to therapy. (VGPR is >90% reduction in serum IgM from baseline)

    Measured: 2 years

  4. Partial Response Rate

    Percentage of patients with partial response (PR) to therapy. (PR is 50-89% reduction in serum IgM from baseline)

    Measured: 2 years

  5. Minimal Response Rate

    Percentage of patients with Minor Responses to therapy. (MR is 25-49% reduction in serum IgM from baseline)

    Measured: 2 years

  6. Stable Disease Rate

    Percentage of patients with Stable disease to therapy. (SD is <25% reduction in serum IgM from baseline).

    Measured: 2 years

  7. Progressive Disease Rate

    Percentage of patients with who experienced disease progression on study. PD is >25% increase in serum IgM from baseline with an absolute increase of at least 500 mg/dL, or progression of clinically significant disease related symptoms. Death from any cause or initiation of a new anti-neoplastic therapy will also be considered a progression event. An increase of 1 cm in any axis for adenopathy, or 2 cm in the craniocaudal axis of the spleen will be considered evidence of progression of extramedullary disease. Development of Bing Neel syndrome, or other extramedullary disease manifestations, as well as disease transformation will be considered as progressive events.

    Measured: From first dose through disease progression, up to 2 years from baseline

  8. Progression Free Survival

    The amount of time between starting treatment and experiencing disease progression. PD is >25% increase in serum IgM from baseline with an absolute increase of at least 500 mg/dL, or progression of clinically significant disease related symptoms. Death from any cause or initiation of a new anti-neoplastic therapy will also be considered a progression event. An increase of 1 cm in any axis for adenopathy, or 2 cm in the craniocaudal axis of the spleen will be considered evidence of progression of extramedullary disease. Development of Bing Neel syndrome, or other extramedullary disease manifestations, as well as disease transformation will be considered as progressive events.

    Measured: From first dose through disease progression, up to 2 years from baseline

  9. Time to Next Therapy (TTNT)

    The amount of time between starting study treatment and initiating a new therapy

    Measured: From first dose through initiation of new therapy, up to 2 years from baseline

  10. Overall Survival

    The number of participants who are still alive at the end of follow-up. Participants were observed for up to 2 years after discontinuing study therapy for survival status.

    Measured: From first dose through death, up to 2 years from baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2019
  2. Study start4 Nov 2019
  3. Primary completion31 Dec 2021
  4. Study completion31 Dec 2021

Why it stopped: Lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04115059
Sponsor's protocol ID
19-305
Status last verified
Sep 2023
First submitted
2 Oct 2019
Last updated
21 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • 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.

    PubMed 36051045

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dasatinib in people with Waldenstrom Macroglobulinemia and DASATINIB, run by Jorge J. Castillo, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With at Least One Treatment-Emergent Adverse Event (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04115059, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2024.

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