NCT04115059

Dasatinib In Waldenström Macroglobulinemia

Terminated Phase 1 Results posted Last updated 21 March 2024

What this trial tests

Phase 1 trial testing Dasatinib in Waldenstrom Macroglobulinemia in 3 participants. Terminated before completion.

Timeline

4 November 2019

Primary endpoint
31 December 2021

31 December 2021

Quick facts

Lead sponsor	Jorge J. Castillo, MD
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3
Start date	4 November 2019
Primary completion	31 December 2021
Estimated completion	31 December 2021
Sites	1 location across United States

Drugs / interventions tested

• Dasatinib (dasatinib) — full drug profile →

Conditions studied

• Waldenstrom Macroglobulinemia — all drugs for Waldenstrom Macroglobulinemia →
• DASATINIB — all drugs for DASATINIB →

Sponsor

Jorge J. Castillo, MD

Who can join

18 and older, any sex, with Waldenstrom Macroglobulinemia or DASATINIB. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With at Least One Treatment-Emergent Adverse Event Primary · 2 years

Count of participants who experience a treatment-emergent adverse event

Group	Value	95% CI
Dasatinib	3

Overall Response Rate Secondary · 2 years

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).

Group	Value	95% CI
Dasatinib	0

Complete Response Rate Secondary · 2 years

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.

Group	Value	95% CI
Dasatinib	0

Very Good Partial Response Rate Secondary · 2 years

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

Group	Value	95% CI
Dasatinib	0

Partial Response Rate Secondary · 2 years

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

Group	Value	95% CI
Dasatinib	0

Minimal Response Rate Secondary · 2 years

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

Group	Value	95% CI
Dasatinib	0

Stable Disease Rate Secondary · 2 years

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

Group	Value	95% CI
Dasatinib	3

Progressive Disease Rate Secondary · From first dose through disease progression, up to 2 years from baseline

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, a

Group	Value	95% CI
Dasatinib	2

Progression Free Survival Secondary · From first dose through disease progression, up to 2 years from baseline

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 manifes

Group	Value	95% CI
Dasatinib	5	0 – 5

Time to Next Therapy (TTNT) Secondary · From first dose through initiation of new therapy, up to 2 years from baseline

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

Group	Value	95% CI
Dasatinib	6	1 – 6

Overall Survival Secondary · From first dose through death, up to 2 years from baseline

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.

Group	Value	95% CI
Dasatinib	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected after dasatinib initiation, through 30 days after the last dose of dasatinib (e.g. 6 months). Participants were observed for overall survival for up to 2 years, or until withdrawal of consent or death.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dasatinib

Serious: 2/3 (67%)

Deaths: 1/3

Serious adverse events (3 terms)

Reaction	System	Dasatinib
Metapneumovirus	Respiratory, thoracic and mediastinal disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Arrhythmia	Cardiac disorders	—

Other adverse events (23 terms — click to expand)

Reaction	System	Dasatinib
Anemia	Blood and lymphatic system disorders	—
Fatigue	General disorders	—
Fever	General disorders	—
Body Aches	Musculoskeletal and connective tissue disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Congestive heart failure	Cardiac disorders	—
Heart failure	Cardiac disorders	—
Abdominal distention	Gastrointestinal disorders	—
Constipation	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Mouth sores	Gastrointestinal disorders	—
Edema	General disorders	—
Fluid overload	General disorders	—
Leg edema	General disorders	—
Withdrawal symptoms	General disorders	—
Neutropenia	Investigations	—
Thrombocytopenia	Investigations	—
Bone pain	Musculoskeletal and connective tissue disorders	—
Dizziness	Nervous system disorders	—
Migraines	Nervous system disorders	—
Insomnia	Psychiatric disorders	—
Post nasal drip	Respiratory, thoracic and mediastinal disorders	—
Sinus congestion	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Metapneumovirus, Febrile neutropenia, Arrhythmia.

Data from ClinicalTrials.gov NCT04115059 adverse events section.

Sponsor's own 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

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Small Molecule NF-κB Pathway Inhibitors in Clinic.
   Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
2. New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.
   Bhatia S, Wang P, Toh A, Thompson EW. · · 2020 · cited 63× · PMID 32391381 · DOI 10.3389/fmolb.2020.00071
3. Management of Waldenström macroglobulinemia in 2020.
   Castillo JJ, Treon SP. · · 2020 · cited 21× · PMID 33275726 · DOI 10.1182/hematology.2020000121
4. A pilot study on dasatinib in patients with Waldenström macroglobulinemia progressing on ibrutinib.
   Castillo JJ, Sarosiek S, Flynn CA, Leventoff C, et al · · 2022 · cited 3× · PMID 36051045 · DOI 10.1002/jha2.493
5. Targeting senescent cells in aging and COVID-19: from cellular mechanisms to therapeutic opportunities.
   Yu Y, Lin K, Wu H, Hu M, et al · · 2024 · cited 1× · PMID 39358480 · DOI 10.1186/s13619-024-00201-1