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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04991103
Recruitment Status : Recruiting
First Posted : August 5, 2021
Last Update Posted : October 22, 2021
Sponsor:
Information provided by (Responsible Party):
Susan Bal, University of Alabama at Birmingham

Brief 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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: DaraVRD Phase 2

Detailed Description:

While AHCT is an important treatment strategy for patients with multiple myeloma, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: All patients with start with 6 cycles of quadruplet induction with daratumumab, lenalidomide, bortezomib and dexamethasone and then depending of their response will receive additional consolidation/maintenance therapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Minimal Residual Disease Response-adapted Deferral of Transplant in Dysproteinemia - MILESTONE Trial
Actual Study Start Date : September 22, 2021
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : August 27, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: Induction - Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DaraVRD)
Quadruplet therapy with DaraVRD in the treatment of newly diagnosed myeloma
Drug: DaraVRD

All patients with newly diagnosed multiple myeloma who was enrolled on the study 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).

Other Names:
  • daratumumab
  • bortezomib
  • lenalidomide
  • dexamethasone




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of patients who was MRD>10-5 that undergo AHCT and attain MRD<10-5. [ Time Frame: Baseline through 10 months ]
    To determine the frequency of conversion from MRD (+) to MRD (-) status with auto-HCT.

  2. Progression free survival [ Time Frame: Baseline through 7 years ]
    To determine the progression free survival (PFS)

  3. Overall survival [ Time Frame: Baseline through 7 years ]
    To determine the frequency of overall survival (OS)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04991103


Contacts
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Contact: Susan Bal, MD 205-934-1908 sbal@uab.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Luciano J Costa, MD, PhD    205-934-1908    ljcosta@uabmc.edu   
Principal Investigator: Susan Bal, MD         
Sub-Investigator: Luciano J Costa, MD, PhD         
Sub-Investigator: Kelly Godby, MD         
Sub-Investigator: Smith Giri, MD         
Sub-Investigator: Lorena De Idiaquez, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Susan Bal, MD University of Alabama at Birmingham
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Responsible Party: Susan Bal, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT04991103    
Other Study ID Numbers: IRB-300007387
First Posted: August 5, 2021    Key Record Dates
Last Update Posted: October 22, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: To be determined.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Susan Bal, University of Alabama at Birmingham:
Minimal residual disease
Autologous stem cell transplantation
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasm, Residual
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Dexamethasone
Lenalidomide
Bortezomib
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists