Hematopoietic Stem Cell Transplant Survivors Study (HTSS Study)
Study Details
Study Description
Brief Summary
The investigators hope to find the proof of principle concept from this pilot study so that the investigators can design a clinical trial based on the results of the explanatory hypothesis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
HSCT survivors are at an increased risk for premature aging. No one has evaluated the biologic markers of premature aging and senescence in HSCT survivors and their correlation with clinical outcomes, lifestyle, and nutrition. The investigators will evaluate age-related changes in HSCT survivors, with specified measures of premature aging, and employ therapeutic opportunities based on targeting senescent cells by conducting the first in-human pilot study of senolytic drugs (in HSCT survivors utilizing a combination of senolytics).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Group 1: Observational Observational only |
Other: Standard of Care - Observation Only
Control Arm - Observation only
|
| Experimental: Group 2: Dasatinib & Quercetin Interventional: The drugs dasatinib and quercetin will be used in this arm |
Drug: Quercetin
Quercetin - take four 250mg capsules daily (total 1000 mg daily) for 3 consecutive days.
Drug: Dasatinib
Dasatinib - take one 100 mg tablet by mouth once daily for 3 consecutive days
Other Names:
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Outcome Measures
Primary Outcome Measures
- Frailty [Day 180]
level of frailty as assessed by FRIED
Eligibility Criteria
Criteria
Inclusion Criteria
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Allogeneic HSCT patients surviving ≥ 1 year post-HSCT
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Diagnosis of both malignant and non-malignant conditions as HSCT indications
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HSCT survivors receiving any type of conditioning chemo/radiotherapy for HSCT
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Ability to provide written and verbal informed consent
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Age ≥ 18 years
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Adequate blood counts i.e. platelets>50,000 per microliter; HB>9/dL, and ANC> 1000 per microliter
Exclusion Criteria
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HSCT survivor with human immunodeficiency virus (HIV) infection
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HSCT survivor with active hepatitis B or C HSCT survivor on any TKI for either Philadelphia chromosome positive cancers or for GVHD treatments or for any other indication (e.g., imatinib for GIST, sorafenib for FLT3+ AML etc)
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HSCT survivor with any post-transplant maintenance chemotherapy
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Post-transplant relapse of cancer
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Active progressive CHRONIC chronic or overlap GVHD (per the NIH chronic GVHD criteria)
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Presence of uncontrolled psychiatric disorder
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Patient unable to give informed consent
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Extremely poor overall prognosis (<6 months as deemed by the primary transplant physician)
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HSCT survivors with confirmed drug addiction
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HSCT survivors with active coronary artery disease (CAD) [including angina] or active congestive heart failure (CHF)
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International HSCT survivors in whom loss to follow-up would be a concern as deemed by primary transplant physician
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Known hypersensitivity or allergy to dasatinib, or quercetin
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Presence of uncontrolled lupus
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Presence of uncontrolled pleural/pericardial effusions or ascites
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Presence of active new cancer (solid or hematologic) except non-melanoma skin cancers
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Presence of progeroid syndromes in family
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Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies.
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Creatinine clearance < 60 mL/min/1.73 m2 based on the Cockcroft-Gault
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Inability to tolerate oral medications
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Total bilirubin>2x upper limit normal (unless deemed to be due to Gilbert's syndrome); AST/ALT>2.5x ULN
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Active progressive ACUTE graft-versus-host disease
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Active progressive OVERLAP graft-versus-host disease
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Patients taking medications that are sensitive substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4(e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are absolutely necessary from infectious disease perspective, then they will be allowed only if the levels are therapeutic. Levels will be checked at baseline and also at day +4 post intervention.
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Patients taking H2-antagonists or proton pump inhibitors.
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Patients on therapeutic doses of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin, factor Xa inhibitors etc).
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On antiplatelet agents (e.g. full dose aspirin, clopidogrel etc.). Baby aspirin if absolutely necessary from cardiac perspective will be allowed.
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On any quinolone antibiotic therapy for treatment or for prevention of infections.
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QTc>450 msec. Common drugs that are well known in prolonging QTc include azithromycin, citalopram, escitalopram, fluconazole, and pentamidine. Baselines EKG will be obtained in each patient and if QTc >450 msec, then they will be excluded from the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Rochester | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Mayo Clinic
Investigators
- Principal Investigator: Suzanne R. Hayman, M.D., Mayo Clinic
- Principal Investigator: Saad J. Kenderian, M.B., Ch.B., Mayo Clinic
- Principal Investigator: Shahrukh K Hashmi, MD, Mayo Clinic
- Principal Investigator: LaTonya Hickson, MD, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 15-004683