Deferring stem cell transplant in newly diagnosed multiple myeloma patients based on minimal residual disease

Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia - MILESTONE Trial

This study is testing if newly diagnosed multiple myeloma patients can safely wait on a stem cell transplant until it's clear they have minimal residual disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Alabama at Birmingham (Academic / other)
• Drugs / interventions: cyclophosphamide
• Locations: 1 site (Birmingham, Alabama)
• Trial ID: NCT04991103 on ClinicalTrials.gov

What this trial studies

This phase II interventional study evaluates the use of minimal residual disease (MRD) assessment through next generation sequencing to determine if autologous hematopoietic stem cell transplantation (AHCT) can be safely deferred in patients with newly diagnosed multiple myeloma. The study aims to reduce the acute and long-term toxicities associated with AHCT by only proceeding with the transplant in patients who show evidence of MRD. By systematically examining MRD response, the study seeks to optimize treatment strategies for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years old with newly diagnosed multiple myeloma and an ECOG performance status of 0-2.

Not a fit: Patients with prior therapy for multiple myeloma or those without measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve the quality of life and long-term outcomes for patients with multiple myeloma by minimizing unnecessary transplants.

How similar studies have performed: While the approach of using MRD to guide treatment decisions is gaining traction, this specific strategy of deferring AHCT based on MRD is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Age \>18 years with no upper age limit with a diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy with Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* No prior therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m2 ) and/or cyclophosphamide up to 1000 mg/m2 administered for management of acute manifestations of multiple myeloma (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment (pre induction). If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available.
* Measurable disease meeting at least one of the following criteria (at screening or prior to pre induction): 1) Serum monoclonal (M) protein ≥1.0 g/dl 2) ≥ 200 mg of M protein/24h in the urine 3) Serum free light chain ≥10 mg/dL and abnormal kappa to lambda ratio.
* Life expectancy ≥ 12 months.
* Adequate organ function - Hepatic function, with serum Alanine Aminotransferase ≤ 2.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 21 days prior to initiation of therapy. Creatinine clearance (CrCl) ≥ 40 mL/minute within 21 days prior to start of therapy.
* Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception during treatment and for 30 days after the last dose of bortezomib. Male subjects must agree to practice contraception and refrain from donating sperm during treatment and for 90 days after the last dose of bortezomib.
* All subjects must agree to comply with and be enrolled in Revlimid Risk Evaluation and Mitigation Strategy (REMS) program.
* Meet institutional criteria for autologous hematopoietic cell transplantation according to investigator's assessment.
* At least 30% ethnic/racial minorities will be included. If necessary, accrual will be held of non-ethnic minority patients while continuing for ethnic minorities in order to ensure at least 30% representation.

Exclusion Criteria:

* Diagnosis of POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes), Waldenstrom's macroglobulinemia.
* Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
* Pregnant or lactating females.
* Patients with uncontrolled human immunodeficiency virus, hepatitis B, hepatitis C. Patients may be eligible with Viral load is undetectable.
* Unstable angina or myocardial infarction within 4 months prior to registration, New York heart association Class II, III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
* Cerebrovascular disease manifested as prior stroke at any time or transient ischemic attack in the 12 months prior to initiation of therapy.
* Non hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or localized thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
* Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 21 days prior to registration.
* Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

Where this trial is running

Birmingham, Alabama

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)

Study contacts

• Principal investigator: Susan Bal, MD — University of Alabama at Birmingham
• Study coordinator: Susan Bal, MD

Conditions Multiple Myeloma; Amyloidosis; Minimal residual disease; Autologous stem cell transplantation