Multiple MyelomaPhase 2MASTERNCT03224507
Monoclonal Antibody-Based Sequential Therapy for Deep Remission in Multiple Myeloma
A Phase 2 study testing KRdD followed by auto-HCT and KRdD only in people with Multiple Myeloma, run by University of Alabama at Birmingham at 4 sites in United States.
Trial summary
Multiple myeloma (MM), a plasma cell disorder, is the second most common hematologic malignancy in the U.S. No standard curative therapy has yet been found. A variety of therapeutic measures including high dose melphalan, induction therapy, and continuous therapy have been used but the goal of complete response… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- KRdD followed by auto-HCT and KRdD only
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Mar 2018to 30 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- No prior MM-directed 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 MM (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment. 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:
- Serum monoclonal (M) protein ≥1.0 g/dl
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- ≥ 200 mg of M protein/24h in the urine
- Serum-free light chain ≥10 mg/dL and abnormal kappa to lambda ratio.
- Life expectancy ≥12 months.
- Adequate hepatic function, with serum ALT ≤ 3.5 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 either measured or calculated using a standard formula (eg. Cockcroft and Gault).
- Written informed consent in accordance with federal, local, and institutional guidelines.
- Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception. Male subjects must agree to practice contraception.
- All subjects must agree to comply with and be enrolled in Revlimid REMS program.
Who cannot join
- Diagnosis of amyloidosis, Crow-Fukase syndrome, Waldenstrom's macroglobulinemia, smoldering MM.
- Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
- Known FEV1 or cDLCO < 50% of predicted.
- Pregnant or lactating females.
- Known human immunodeficiency virus infection.
- Active hepatitis B (Hepatitis B core antibody positive and subsequent Hepatitis B surface antigen positive or Hepatitis B DNA positive) or C infection (Hepatitis C antibody positive and subsequent detectable viral load).
Show all 14Show fewer
- 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 TIA 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.
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 21 days prior to registration.
- Contraindication or intolerance to required supportive care medications (Aspirin and Acyclovir).
- 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
4 sites in 1 country.
United States4 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Wisconsin, school of medicine and public health
Madison, Wisconsin, 53792
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Oregon Health and Science University
Portland, Oregon, 97239
About this study
Official title: Monoclonal Antibody-Based Sequential Therapy for Deep Remission in Multiple Myeloma - MASTER Trial
Multiple myeloma (MM), a plasma cell disorder, is the second most common hematologic malignancy in the U.S. No standard curative therapy has yet been found. A variety of therapeutic measures including high dose melphalan, induction therapy, and continuous therapy have been used but the goal of complete response without relapse has not been achieved. More active treatment regimens and better tools for response assessment are needed.
Read the detailed description
This trial will assess the safety and efficacy of an induction therapy using the combination of dexamethasone, lenalidomide (revlimid), daratumumab (Darzalex) and carfilzomib (Kyprolis) to treat patients with newly diagnosed multiple myeloma. The therapy with KRdD (Kyprolis, Revlimid, dexamethasone, Darzalex) will be followed by autologous hematopoietic cell transplantation (auto-HCT) and KRdD consolidation. Duration of therapy will be guided by eradication of minimal residual disease (MRD). The hypothesis is that the KRdD therapy particularly in combination with the auto-HCT will be safe and lead to deep remission. Patients who become MRD- will discontinue therapy (no maintenance therapy) and be actively monitored for resurgence of MRD or clinical relapse.
- Conditions
- Multiple Myeloma
- Being tested
- KRdD followed by auto-HCT, KRdD only
- Keywords
- multiple myeloma, induction therapy, autologous hematopoietic cell transplantation, KRdD, Daratumumab, Carfilzomib, Lenalidomide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRdD followed by auto-HCTDrug
Also called KRdD = Kyprolis (Carfilzomib), Revlimid (Lenalidomide), dexamethasone, Darzalex (Daratumumab)
Dosages of each drug will vary depending on therapy type and cycle number. KRdD therapy will be followed by autologous hematopoietic cell transplantation and KRdD consolidation.
KRdD onlyDrug
Also called KRdD = Kyprolis (Carfilzomib), Revlimid (Lenalidomide), dexamethasone, Darzalex (Daratumumab)
Dosages of each drug will vary depending on therapy type and cycle number. KRdD therapy will not be followed by autologous hematopoietic cell transplantation but will proceed with KRdD consolidation.
| Study group | Role | What they receive |
|---|---|---|
| KRdD followed by auto-HCT | Experimental | Cycle 1-Dexamethasone 40mg orally days 1/8/15/22; Lenalidomide 25mg orally days 1-21; Carfilzomib 20mg/m2 days 8/9 then 36mg/m2 venous days 15/16; Daratumumab 16mg/kg venous days 1/8/15/22 (KRd-Dara). Cycle 2 the same except Carfilzomib 36mg/m2 venous days 1/2/8/9/15/16. Cycles 3,4 the same but no Daratumumab Days 8 and 22. Dosage adjusted for last tolerated dose (LTD). Following induction therapy, auto-HCT is done (consolidation 1), then up to two 4-cycle blocks of KRd-Dara consolidation (consolidations 2 and 3). Minimum residual disease (MRD) checked after each phase. Patients with confirmed MRD(-) at or after consolidation 1 will not undergo maintenance and will be actively monitored for resurgence of MRD or clinical relapse. After consolidation if MRD+ patients will undergo standard of care lenalidomide maintenance. Receives: Drug: KRdD followed by auto-HCT |
| KRdD only | Experimental | Cycle 1-Dexamethasone 40mg orally days 1/8/15/22; Lenalidomide 25mg orally days 1-21; Carfilzomib 20mg/m2 days 8/9 then @ 36mg/m2 venous days 15/16; Daratumumab 16mg/kg venous days 1/8/15/22. Cycle 2 the same except Carfilzomib 36mg/m2 venous days 1/2/8/9/15/16. Cycles 3,4 the same but no Daratumumab Day 22. Dosage adjusted for last tolerated dose (LTD). Following induction therapy, Following induction therapy, patients will receive up to three 4-cycle blocks of KRd-Dara consolidation (consolidations 1, 2 and 3). Minimum residual disease (MRD) checked after each phase. Patients with confirmed MRD(-) at or after consolidation 1 will not undergo maintenance and will be actively monitored for resurgence of MRD or clinical relapse. After consolidation if MRD+ patients will undergo standard of care lenalidomide maintenance. Receives: Drug: KRdD only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients With MRD(-) Remissions at the Completion of Consolidation Therapy
The primary endpoint of MRD(-) rate, or percentage of patients with MRD(-) remissions, will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences.
Measured: Baseline until MRD(-) is reached estimated to be up to 15 months.
Secondary outcomes (7)
Serious Adverse Events (SAEs) From the KRdD Treatment
The Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be used for this assessment. SAEs include events that are Grade 3 and above; non-serious events are Grades 1-2.
Measured: Baseline until the progression of disease or MRD(-) status up to an estimated 15 months.
Percentage of Patients With MRD(-) Status at the Completion of Induction Therapy
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences.
Measured: Baseline until MRD(-) status estimated at 6 months or until disease progression
Percentage of Patients With Auto-HCT That Convert From Positive to Negative MRD
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences.
Measured: From baseline up to an estimated 9 months
Percentage of Patients Achieving Complete Remission Following Complete Therapy
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences. Complete therapy incorporates induction and consolidation therapy.
Measured: Baseline up to 15 months
Percentage of Patients That Convert From MRD(-) to MRD(+) Following Treatment Discontinuation
The primary endpoint of MRD(-) rate will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences.
Measured: Baseline to 2 years
Progression-free Survival
Progression-free survival is defined as the interval from the start of therapy to the earliest occurrence of the following: disease progression, initiation of anti-myeloma therapy that is not an accepted maintenance therapy of lenalidomide or death from any cause. Kaplan-Meier methods will used.
Measured: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
Overall Survival
Overall survival is defined as the time from date of study enrollment until death from any cause.
Measured: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start14 Mar 2018
- Primary completion1 May 2023
- Study completion30 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study has four cycles (28-days each) of drug therapy prior to being evaluated for auto-HCT. After the completion of induction therapy, the patient will be evaluated for a transplant of their own hematopoietic stem cells. If, after the transplant, the patient still has detectable multiple myeloma, the patient will proceed to a series of consolidation blocks, up to three, consisting of four cycles of the KRdD at specified dosages and time frames. After completion of consolidation therapy, maintenance therapy will begin until disease progression or intolerance.
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Janssen Scientific Affairs, LLC
- Responsible party
- Principal investigator, Luciano Jose Costa, MD, University of Alabama at Birmingham
- Investigators
- Luciano J Costa, MD, PhD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224507
- Sponsor's protocol ID
- F170525008 (UAB 1735)
- Acronym
- MASTER
- Status last verified
- Nov 2023
- First submitted
- 10 Jul 2017
- Last updated
- 24 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ravi G, Dhakal B, Callander NS, Medvedova E, Dholaria BR, Godby KN, Bal S, Huls F, Silbermann RW, Costa LJ. Redefining functional high-risk multiple myeloma in the context of upfront quadruplet therapy and autologous stem cell transplantation. Cancer. 2026 Jul 15;132(14):e70478. doi: 10.1002/cncr.70478.
PubMed 42473325Giri S, Dhakal B, Callander NS, Medvedova E, Godby K, Dholaria BR, Bal S, Ravi G, Chhabra S, Silbermann RW, Costa L. Optimal MRD-based end point to support response-adapted treatment cessation in newly diagnosed multiple myeloma. Blood. 2025 Aug 7;146(6):707-716. doi: 10.1182/blood.2024027674.
PubMed 40193714Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
PubMed 38649340Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, Silbermann R, Dhakal B, Bal S, Giri S, D'Souza A, Hall AC, Hardwick P, Omel J, Cornell RF, Hari P, Callander NS. Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial. Lancet Haematol. 2023 Nov;10(11):e890-e901. doi: 10.1016/S2352-3026(23)00236-3. Epub 2023 Sep 27.
PubMed 37776872Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, Silbermann R, Dhakal B, Bal S, Giri S, D'Souza A, Hall A, Hardwick P, Omel J, Cornell RF, Hari P, Callander NS. Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2022 Sep 1;40(25):2901-2912. doi: 10.1200/JCO.21.01935. Epub 2021 Dec 13.
PubMed 34898239
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monoclonal Antibody-Based Sequential Therapy for Deep Remission in Multiple Myeloma - MASTER Trial
- ClinicalTrials.gov ID
- NCT03224507
- Acronym / sponsor ID
- MASTER / F170525008 (UAB 1735)
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, induction therapy, autologous hematopoietic cell transplantation, KRdD, Daratumumab, Carfilzomib, Lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Amgen, Janssen Scientific Affairs, LLC
- Study start
- 14 Mar 2018 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Posted 22 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple myeloma (MM), a plasma cell disorder, is the second most common hematologic malignancy in the U.S. No standard curative therapy has yet been found. A variety of therapeutic measures including high dose melphalan, induction therapy, and continuous therapy have been used but the goal of complete response without relapse has not been achieved. More active treatment regimens and better tools for response assessment are needed.
Detailed description
This trial will assess the safety and efficacy of an induction therapy using the combination of dexamethasone, lenalidomide (revlimid), daratumumab (Darzalex) and carfilzomib (Kyprolis) to treat patients with newly diagnosed multiple myeloma. The therapy with KRdD (Kyprolis, Revlimid, dexamethasone, Darzalex) will be followed by autologous hematopoietic cell transplantation (auto-HCT) and KRdD consolidation. Duration of therapy will be guided by eradication of minimal residual disease (MRD). The hypothesis is that the KRdD therapy particularly in combination with the auto-HCT will be safe and lead to deep remission. Patients who become MRD- will discontinue therapy (no maintenance therapy) and be actively monitored for resurgence of MRD or clinical relapse.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study has four cycles (28-days each) of drug therapy prior to being evaluated for auto-HCT. After the completion of induction therapy, the patient will be evaluated for a transplant of their own hematopoietic stem cells. If, after the transplant, the patient still has detectable multiple myeloma, the patient will proceed to a series of consolidation blocks, up to three, consisting of four cycles of the KRdD at specified dosages and time frames. After completion of consolidation therapy, maintenance therapy will begin until disease progression or intolerance.
| Arm | Type | Receives |
|---|---|---|
| KRdD followed by auto-HCT | Experimental | Drug: KRdD followed by auto-HCTCycle 1-Dexamethasone 40mg orally days 1/8/15/22; Lenalidomide 25mg orally days 1-21; Carfilzomib 20mg/m2 days 8/9 then 36mg/m2 venous days 15/16; Daratumumab 16mg/kg venous days 1/8/15/22 (KRd-Dara). Cycle 2 the same except Carfilzomib 36mg/m2 venous days 1/2/8/9/15/16. Cycles 3,4 the same but no Daratumumab Days 8 and 22. Dosage adjusted for last tolerated dose (LTD). Following induction therapy, auto-HCT is done (consolidation 1), then up to two 4-cycle blocks of KRd-Dara consolidation (consolidations 2 and 3). Minimum residual disease (MRD) checked after each phase. Patients with confirmed MRD(-) at or after consolidation 1 will not undergo maintenance and will be actively monitored for resurgence of MRD or clinical relapse. After consolidation if MRD+ patients will undergo standard of care lenalidomide maintenance. |
| KRdD only | Experimental | Drug: KRdD onlyCycle 1-Dexamethasone 40mg orally days 1/8/15/22; Lenalidomide 25mg orally days 1-21; Carfilzomib 20mg/m2 days 8/9 then @ 36mg/m2 venous days 15/16; Daratumumab 16mg/kg venous days 1/8/15/22. Cycle 2 the same except Carfilzomib 36mg/m2 venous days 1/2/8/9/15/16. Cycles 3,4 the same but no Daratumumab Day 22. Dosage adjusted for last tolerated dose (LTD). Following induction therapy, Following induction therapy, patients will receive up to three 4-cycle blocks of KRd-Dara consolidation (consolidations 1, 2 and 3). Minimum residual disease (MRD) checked after each phase. Patients with confirmed MRD(-) at or after consolidation 1 will not undergo maintenance and will be actively monitored for resurgence of MRD or clinical relapse. After consolidation if MRD+ patients will undergo standard of care lenalidomide maintenance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age >18 years with no upper age limit
- Diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- No prior MM-directed 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 MM (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment. 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:
Key exclusion criteria (14 listed)
- Diagnosis of amyloidosis, Crow-Fukase syndrome, Waldenstrom's macroglobulinemia, smoldering MM.
- Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
- Known FEV1 or cDLCO < 50% of predicted.
- Pregnant or lactating females.
- Known human immunodeficiency virus infection.
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 |
|---|---|---|
| KRdD followed by auto-HCTAlso: KRdD = Kyprolis (Carfilzomib), Revlimid (Lenalidomide), dexamethasone, Darzalex (Daratumumab)Dosages of each drug will vary depending on therapy type and cycle number. KRdD therapy will be followed by autologous hematopoietic cell transplantation and KRdD consolidation. | Drug | KRdD followed by auto-HCT |
| KRdD onlyAlso: KRdD = Kyprolis (Carfilzomib), Revlimid (Lenalidomide), dexamethasone, Darzalex (Daratumumab)Dosages of each drug will vary depending on therapy type and cycle number. KRdD therapy will not be followed by autologous hematopoietic cell transplantation but will proceed with KRdD consolidation. | Drug | KRdD only |
Primary outcome
Percentage of Patients With MRD(-) Remissions at the Completion of Consolidation Therapy
Time frame: Baseline until MRD(-) is reached estimated to be up to 15 months.
The primary endpoint of MRD(-) rate, or percentage of patients with MRD(-) remissions, will be estimated along with two-sided 95% confidence interval using Clopper-Pearson exact method. Simon's optimal two-stage design will be utilized in determining the rate of MRD(-) cases. MRD assessment will be done with ClonoSEQ to identify myeloma-specific sequences.
7 secondary outcomes
Serious Adverse Events (SAEs) From the KRdD Treatment
Time frame: Baseline until the progression of disease or MRD(-) status up to an estimated 15 months.
Percentage of Patients With MRD(-) Status at the Completion of Induction Therapy
Time frame: Baseline until MRD(-) status estimated at 6 months or until disease progression
Percentage of Patients With Auto-HCT That Convert From Positive to Negative MRD
Time frame: From baseline up to an estimated 9 months
Percentage of Patients Achieving Complete Remission Following Complete Therapy
Time frame: Baseline up to 15 months
Percentage of Patients That Convert From MRD(-) to MRD(+) Following Treatment Discontinuation
Time frame: Baseline to 2 years
Progression-free Survival
Time frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
Overall Survival
Time frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42473325Ravi G, Dhakal B, Callander NS, Medvedova E, Dholaria BR, Godby KN, Bal S, Huls F, Silbermann RW, Costa LJ. Redefining functional high-risk multiple myeloma in the context of upfront quadruplet therapy and autologous stem cell transplantation. Cancer. 2026 Jul 15;132(14):e70478. doi: 10.1002/cncr.70478.
- Derived from this study: PubMed 40193714Giri S, Dhakal B, Callander NS, Medvedova E, Godby K, Dholaria BR, Bal S, Ravi G, Chhabra S, Silbermann RW, Costa L. Optimal MRD-based end point to support response-adapted treatment cessation in newly diagnosed multiple myeloma. Blood. 2025 Aug 7;146(6):707-716. doi: 10.1182/blood.2024027674.
- Derived from this study: PubMed 38649340Callander NS, Silbermann R, Kaufman JL, Godby KN, Laubach J, Schmidt TM, Sborov DW, Medvedova E, Reeves B, Dhakal B, Rodriguez C, Chhabra S, Chari A, Bal S, Anderson LD Jr, Dholaria BR, Nathwani N, Hari P, Shah N, Bumma N, Holstein SA, Costello C, Jakubowiak A, Wildes TM, Orlowski RZ, Shain KH, Cowan AJ, Pei H, Cortoos A, Patel S, Lin TS, Giri S, Costa LJ, Usmani SZ, Richardson PG, Voorhees PM. Daratumumab-based quadruplet therapy for transplant-eligible newly diagnosed multiple myeloma with high cytogenetic risk. Blood Cancer J. 2024 Apr 22;14(1):69. doi: 10.1038/s41408-024-01030-w.
- Derived from this study: PubMed 37776872Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, Silbermann R, Dhakal B, Bal S, Giri S, D'Souza A, Hall AC, Hardwick P, Omel J, Cornell RF, Hari P, Callander NS. Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial. Lancet Haematol. 2023 Nov;10(11):e890-e901. doi: 10.1016/S2352-3026(23)00236-3. Epub 2023 Sep 27.
- Derived from this study: PubMed 34898239Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, Silbermann R, Dhakal B, Bal S, Giri S, D'Souza A, Hall A, Hardwick P, Omel J, Cornell RF, Hari P, Callander NS. Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2022 Sep 1;40(25):2901-2912. doi: 10.1200/JCO.21.01935. Epub 2021 Dec 13.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Luciano J Costa, MD, PhD principal investigator
University of Alabama at Birmingham
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KRdD followed by auto-HCT and KRdD only in people with Multiple Myeloma, run by University of Alabama at Birmingham at 4 sites 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 14 inclusion and 14 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: finished, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Yes. Results are posted in the registry (first posted 22 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Patients With MRD(-) Remissions at the Completion of Consolidation Therapy (time frame: Baseline until MRD(-) is reached estimated to be up to 15 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03224507, which also lists 5 linked publications.
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 24 Nov 2023.