Multiple MyelomaPhase 2NCT04991103
Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia (MILESTONE)
A Phase 2 study testing DaraVRD/DaraVCD in people with Multiple Myeloma and Amyloidosis, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Amyloidosis
- What is being tested?
- DaraVRD/DaraVCD
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2021to 27 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Luciano J Costa, MD, PhD, 205-934-1908, ljcosta@uabmc.edu
Susan Bal, MD
About this study
Official title: Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia - MILESTONE Trial
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).
Read the detailed description
While AHCT is an important treatment strategy for patients with plasma cell disorders, from a safety standpoint, AHCT is associated with both acute toxicities that reduce quality of life and long-term toxicities that may limit life expectancy for some patients. Additionally its benefit in patients without evidence of minimal residual disease (MRD) is unknown.
We propose to examine MRD response as a strategy to defer AHCT in a systematic manner.
- Conditions
- Multiple Myeloma, Amyloidosis
- Being tested
- DaraVRD/DaraVCD
- Keywords
- Minimal residual disease, Autologous stem cell transplantation
- Medical subject headings
- Multiple Myeloma, Amyloidosis, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaraVRD/DaraVCDDrug
Also called daratumumab, bortezomib, lenalidomide, dexamethasone
Patients in Cohort A with newly diagnosed multiple myeloma will receive six cycles of combination quadruplet therapy (DaraVRD).
Six 28-day induction cycles of oral lenalidomide (25 mg daily on days 1-21), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22).
Patients in Cohort B with newly diagnosed amyloidosis will receive six cycles of combination quadruplet therapy (DaraVCD).
Six 28-day induction cycles of IV cyclophosphamide (300 mg/m2 on days 1, 8, 15, 22), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22).
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab, Bortezomib, Dexamethasone with Lenalidomide/Cyclophosphamide | Experimental | Quadruplet therapy in the treatment of newly diagnosed myeloma and AL amyloidosis Receives: Drug: DaraVRD/DaraVCD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who are able to attain MRD<10-5 by next generation sequencing after 6 cycles of Dara-VRD and defer AHCT.
To determine the feasibility of utilizing post-induction MRD to inform transplant utilization.
Measured: Baseline through 6 months
Secondary outcomes (3)
Number of patients who was MRD>10-5 that undergo AHCT and attain MRD<10-5.
To determine the frequency of conversion from MRD (+) to MRD (-) status with auto-HCT.
Measured: Baseline through 10 months
Progression free survival
To determine the progression free survival (PFS)
Measured: Baseline through 7 years
Overall survival
To determine the frequency of overall survival (OS)
Measured: Baseline through 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start22 Sep 2021
- Primary completion1 Jan 2027 (estimated)
- Study completion27 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- All patients with start with 6 cycles of quadruplet induction (Cohort A: daratumumab, lenalidomide, bortezomib and dexamethasone; Cohort B: daratumumab, cyclophosphamide, bortezomib and dexamethasone) and then depending of their response will receive additional consolidation/maintenance therapy.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susan Bal, University of Alabama at Birmingham
- Investigators
- Susan Bal, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04991103
- Sponsor's protocol ID
- IRB-300007387
- Status last verified
- Dec 2025
- First submitted
- 27 Jul 2021
- Last updated
- 31 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: To be determined.
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia - MILESTONE Trial
- ClinicalTrials.gov ID
- NCT04991103
- Acronym / sponsor ID
- IRB-300007387
- Conditions
- Multiple Myeloma, Amyloidosis
- Keywords
- Minimal residual disease, Autologous stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 22 Sep 2021 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 27 Aug 2028 (estimated)
- First posted
- 5 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
While AHCT is an important treatment strategy for patients with plasma cell disorders, from a safety standpoint, AHCT is associated with both acute toxicities that reduce quality of life and long-term toxicities that may limit life expectancy for some patients. Additionally its benefit in patients without evidence of minimal residual disease (MRD) is unknown.
We propose to examine MRD response as a strategy to defer AHCT in a systematic manner.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients with start with 6 cycles of quadruplet induction (Cohort A: daratumumab, lenalidomide, bortezomib and dexamethasone; Cohort B: daratumumab, cyclophosphamide, bortezomib and dexamethasone) and then depending of their response will receive additional consolidation/maintenance therapy.
| Arm | Type | Receives |
|---|---|---|
| Daratumumab, Bortezomib, Dexamethasone with Lenalidomide/Cyclophosphamide | Experimental | Drug: DaraVRD/DaraVCDQuadruplet therapy in the treatment of newly diagnosed myeloma and AL amyloidosis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaraVRD/DaraVCDAlso: daratumumab, bortezomib, lenalidomide, dexamethasonePatients in Cohort A with newly diagnosed multiple myeloma will receive six cycles of combination quadruplet therapy (DaraVRD). Six 28-day induction cycles of oral lenalidomide (25 mg daily on days 1-21), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22). Patients in Cohort B with newly diagnosed amyloidosis will receive six cycles of combination quadruplet therapy (DaraVCD). Six 28-day induction cycles of IV cyclophosphamide (300 mg/m2 on days 1, 8, 15, 22), subcutaneous bortezomib (1.3 mg/m2 on days 1, 8, 15, 22), subcutaneous daratumumab (1800 mg on days 1, 8, 15, 22 of cycles 1-2 and days 1, 15 for cycles 3-6), and oral dexamethasone (40 mg on days 1, 8, 15, and 22). | Drug | Daratumumab, Bortezomib, Dexamethasone with Lenalidomide/Cyclophosphamide |
Primary outcome
Number of patients who are able to attain MRD<10-5 by next generation sequencing after 6 cycles of Dara-VRD and defer AHCT.
Time frame: Baseline through 6 months
To determine the feasibility of utilizing post-induction MRD to inform transplant utilization.
3 secondary outcomes
Number of patients who was MRD>10-5 that undergo AHCT and attain MRD<10-5.
Time frame: Baseline through 10 months
Progression free survival
Time frame: Baseline through 7 years
Overall survival
Time frame: Baseline through 7 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- Individual participant dataSharing planned: No. To be determined.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Susan Bal, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing DaraVRD/DaraVCD in people with Multiple Myeloma and Amyloidosis, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Susan Bal, MD (205-934-1908, sbal@uab.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients who are able to attain MRD<10-5 by next generation sequencing after 6 cycles of Dara-VRD and defer AHCT. (time frame: Baseline through 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.