Dasatinib and quercetin plus preparation chemotherapy before CAR-T for relapsed or refractory multiple myeloma

DART: Phase II Study of Dasatinib and Quercetin in Patients With Relapsed, Refractory Multiple Myeloma Receiving CAR-T Therapy

This phase II test will see whether adding dasatinib and quercetin to preparation chemotherapy and CAR-T cell therapy helps people with relapsed or refractory multiple myeloma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (Academic / other)
• Drugs / interventions: dasatinib, CAR-T, CAR T, chimeric antigen receptor, Chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT06940297 on ClinicalTrials.gov

What this trial studies

This single-arm phase II trial gives adults with heavily pretreated relapsed or refractory multiple myeloma cyclophosphamide and fludarabine to prepare for CAR-T, along with dasatinib and quercetin, followed by infusion of ciltacabtagene autoleucel. Patients undergo leukapheresis for T-cell collection, CAR-T manufacturing, and scheduled biospecimen collection including bone marrow aspiration and biopsy. The study monitors safety, tolerability, and anti-myeloma responses over follow-up visits at the treatment center. The trial is conducted at Mayo Clinic in Rochester in collaboration with the National Cancer Institute.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory multiple myeloma after at least three prior lines including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody, who are candidates for ciltacabtagene autoleucel and have ECOG performance status 0–2.

Not a fit: Patients with earlier-stage disease, those who are not eligible for CAR-T manufacturing, or those with severe organ dysfunction are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase the depth and durability of responses to CAR-T therapy in heavily pretreated myeloma patients.

How similar studies have performed: BCMA-targeted CAR-T therapies such as ciltacabtagene autoleucel have produced strong responses in relapsed/refractory myeloma, but combining CAR-T with dasatinib and quercetin is relatively novel and has limited clinical evidence to date.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Relapsed or refractory multiple myeloma who has had at least 3 prior lines of therapies including a proteasome inhibitor, immunomodulatory drug (IMiD) and anti-CD38 monoclonal antibody (mAb)
* Ciltacabtagene autoleucel (Carvykti) available for patient
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
* Life expectancy ≥ 12 weeks
* Hemoglobin ≥ 8.0 g/dL (obtained ≤ 14 days prior to registration)
* Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (obtained ≤ 14 days prior to registration)
* Platelet count ≥ 50,000/mm\^3 (obtained ≤ 14 days prior to registration)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration)

  * Note: Patients with Gilbert's syndrome must have a total bilirubin of ≤ 3 x ULN (obtained ≤ 14 days prior to registration)
* Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2 x ULN (obtained ≤ 14 days prior to registration)
* Alkaline phosphatase ≤ 1.5 x ULN (obtained ≤ 14 days prior to registration)
* Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration)
* Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only

  * Note: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry and for the duration of study participation and for at least 30 days after the last dose of study drug
* Provide written informed consent
* Willingness to provide mandatory blood and bone marrow specimens for correlative research
* Willingness to provide mandatory bone marrow cores and/or tissue specimens for correlative research
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

* Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or AL amyloidosis
* Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment.

  * EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 1 month since completion of prior treatment
* Any of the following because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects:

  * Pregnant persons
  * Nursing persons
  * Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
* Major surgery ≤ 28 days prior to registration
* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Immunocompromised patients and patients known to be HIV positive.

  * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, or those currently receiving antiretroviral therapy with good control of HIV, are eligible for this trial
* Evidence of cardiovascular disease risk, as defined by any of the following:

  * Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block
  * History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of screening.
  * Class III or IV heart failure as defined by the New York Heart Association functional classification system
  * Uncontrolled hypertension
  * History of life-threatening ventricular arrhythmias
  * QTC interval \[electrocardiogram (ECG)\] ≥ 450 msec
* Uncontrolled intercurrent illness including, but not limited to:

  * Ongoing or active infection
  * Any medical condition that would make participation unduly hazardous
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Live vaccine ≤ 6 weeks prior to registration
* Has taken a strong inhibitor or inducer of CYP3A4/5, including grapefruit, St. John's Wort or related products ≤ 14 days prior to registration.

  * Note: If required, patients may receive a short course of strong inhibitors or inducers for treatment of symptoms, but dasatinib dose must be adjusted as indicated
* Known hypersensitivity or allergy to dasatinib or quercetin
* Patients on therapeutic doses of anticoagulants (e.g. warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc).
* On antiplatelet agents (e.g. full dose aspirin, clopidogrel etc.)

  * NOTE: Baby aspirin, if necessary for cardioprotection, will be allowed
* On quinolone antibiotic therapy for treatment or for prevention of infections products ≤10 days prior to registration

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Yi Lin, MD, PhD — Mayo Clinic
• Study coordinator: Clinical Trials Referral Office

Conditions Recurrent Multiple Myeloma; Refractory Multiple Myeloma