RECRUITING

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

Conditions

Multiple Myeloma Amyloidosis Minimal residual disease Autologous stem cell transplantation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II interventional study evaluating the use of minimal residual disease by next generation sequencing to defer autologous hematopoietic stem cell transplantation (AHCT) in patients with newly diagnosed multiple myeloma (cohort A) and amyloidosis (cohort B).

Official Title

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

Quick Facts

Study Start:2021-09-22

Study Completion:2028-08-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04991103

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Susan Bal, MD

CONTACT

205-934-1908

sbal@uab.edu

Principal Investigator

Susan Bal, MD

PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

Susan Bal, MD, PRINCIPAL_INVESTIGATOR, University of Alabama at Birmingham

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-22

Study Completion Date2028-08-27

Study Record Updates

Study Start Date2021-09-22

Study Completion Date2028-08-27

Terms related to this study

Keywords Provided by Researchers

Minimal residual disease
Autologous stem cell transplantation

Additional Relevant MeSH Terms

Multiple Myeloma
Amyloidosis