Sequential Therapy in Multiple Myeloma Guided by MRD Assessments

NCT05231629 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UAB-2110764007957MMY2005
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 10

Brief Summary

This research study will determine the proportion of patients with lowest minimal residual disease (MRD) response obtainable after receiving 6 cycles of study treatment. Minimal residual disease is multiple myeloma cells below the level of 1 cancer cell out of 100,000 in the bone marrow. For patients who become MRD "negative" (i.e. less than 1 cancer cell out of 100,000) at the end of 6 cycles of therapy, this study will study if that good response can be maintained with 3 additional cycles of treatment instead of use of autologous hematopoietic cell transplantation (AHCT). For patients who are MRD "positive" at the end of 6 cycles of therapy, this study will answer whether more patients can become and remain MRD "negative" with AHCT plus teclistamab in combination with daratumumab when compared with patients who undergo AHCT followed by lenalidomide (an established anti-myeloma drug) plus daratumumab.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Depth of response obtained with 6 cycles of Dara-VRd

  For the primary objective "for all patients" to describe the depth of response obtained with 6 cycles of Dara-VRd and the corresponding endpoint of MRD negativity at end of induction all patients with MRD evaluable

  6 months

• Sustained MRD negativity

  MRD \<10-5 assessed before and after 13 cycles of maintenance

  18 months

Secondary Outcomes (3)

• Progression-free survival

  60 months

• Overall Survival

  60 months

• Cumulative incidence of MRD resurgence or progression

  60 months

Study Arms (5)

Arm A

EXPERIMENTAL

3 cycles of Dara-VRd intensification followed by 13 cycles of Dara-R maintenance in MRD negative patients

Drug: Dara-VRd intensification, Dara-R maintenance

Arm B

ACTIVE COMPARATOR

AHCT intensification followed by 13 cycles of Dara-R maintenance in MRD negative patients

Drug: AHCT intensification, Dara-R maintenance

Arm C

EXPERIMENTAL

AHCT intensification, 3 cycles of Dara-Tec consolidation and 13 cycles of Dara-Tec maintenance in MRD positive patients

Drug: AHCT intensification, Tec-Dara consolidation, Tec-Dara maintenance

Arm D

ACTIVE COMPARATOR

AHCT intensification, 3 cycles of Dara-R consolidation and 13 cycles of Dara-R maintenance in MRD positive patients

Drug: AHCT intensification, Dara-R consolidation, Dara-R maintenance

Arm M

OTHER

Induction - 6 cycles of Dara-VRd in all participants

Drug: Dara-VRd induction

Interventions

Dara-VRd intensification, Dara-R maintenance DRUG

Eligible patients are enrolled in arm M for induction therapy, corresponding to 6 cycles of Dara-VRd. Upon confirmation of adequate hematopoietic cell collection and result of MRD1 patients will undergo 1:1 randomization according to the MRD-assigned cohort • MRD negative cohort - Patients will be randomized between arm A (3 cycles of Dara-VRd intensification followed by 13 cycles of Dara-R maintenance) and arm B (AHCT intensification followed by 13 cycles of Dara-R maintenance) for intensification and maintenance

Also known as: darzalex, velcade, revlimid, dexamethasone

Arm A

AHCT intensification, Dara-R maintenance DRUG

Eligible patients are enrolled in arm M for induction therapy, corresponding to 6 cycles of Dara-VRd. Upon confirmation of adequate hematopoietic cell collection and result of MRD1 patients will undergo 1:1 randomization according to the MRD-assigned cohort • MRD negative cohort - Patients will be randomized between arm A (3 cycles of Dara-VRd intensification followed by 13 cycles of Dara-R maintenance) and arm B (AHCT intensification followed by 13 cycles of Dara-R maintenance) for intensification and maintenance

Also known as: melphalan, darzalex, revlimid

Arm B

AHCT intensification, Tec-Dara consolidation, Tec-Dara maintenance DRUG

Eligible patients are enrolled in arm M for induction therapy, corresponding to 6 cycles of Dara-VRd. Upon confirmation of adequate hematopoietic cell collection and result of MRD1 patients will undergo 1:1 randomization according to the MRD-assigned cohort. MRD positive cohort - Patients will be randomized between arm C (AHCT intensification, 3 cycles of Dara-Tec consolidation and 13 cycles of Dara-Tec maintenance) and arm D (AHCT intensification, 3 cycles of Dara-R consolidation and 13 cycles of Dara-R maintenance) for intensification, consolidation and maintenance.

Also known as: melphalan, teclistamab, darzalex

Arm C

AHCT intensification, Dara-R consolidation, Dara-R maintenance DRUG

Eligible patients are enrolled in arm M for induction therapy, corresponding to 6 cycles of Dara-VRd. Upon confirmation of adequate hematopoietic cell collection and result of MRD1 patients will undergo 1:1 randomization according to the MRD-assigned cohort. MRD positive cohort - Patients will be randomized between arm C (AHCT intensification, 3 cycles of Dara-Tec consolidation and 13 cycles of Dara-Tec maintenance) and arm D (AHCT intensification, 3 cycles of Dara-R consolidation and 13 cycles of Dara-R maintenance) for intensification, consolidation and maintenance.

Also known as: melphalan, darzalex, revlimid

Arm D

Dara-VRd induction DRUG

Patients undergo induction therapy with 6 cycles of daratumumab, bortezomib, lenalidomide and dexamethasone

Also known as: darzalex, velcade, revlimid, dexamethasone

Arm M

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age\>18 years with no upper age limit
• Newly diagnosed multiple myeloma with indication for initiation of therapy.
• 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 and/or lenalidomide (up to 21 days of therapy) administered 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):
• Serum monoclonal (M) protein ≥1.0 g/dl (≥0.5 g/dl if IgA, IgD, IgE or IgM multiple myeloma)
• ≥ 200 mg of M protein/24h in the urine
• Difference between affected and unaffected free light chain ≥10 mg/dL with abnormal kappa to lambda ratio.
• Have clinical laboratory values meeting the following criteria during the Screening Phase and also at start of administration of study treatment
• Hemoglobin ≥7 g/dL (≥4.65 mmol/L; without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted)
• Platelets ≥75×10\^9/L in participants in whom \<50% of bone marrow nucleated cells are plasma cells and ≥50×10\^9/L in participants in whom
• % of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test)
• Absolute neutrophil count ≥1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF and for 14 days for pegylated G CSF)
• AST and ALT ≤2.5×ULN
• eGFR ≥30 mL/min based on Modified Diet in Renal Disease Formula calculation or creatine clearance measured by a 24-hour urine collection

You may not qualify if:

• Diagnosis of Plasma cell leukemia, primary light chain amyloidosis, POEMS, or Waldenstrom's macroglobulinemia.
• Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts)
• Prior or concurrent exposure to any of the following:
• Teclistamab or any anti-BCMA therapy
• Daratumumab or any anti-CD38 therapy
• Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less
• Investigational vaccine within 4 weeks
• Live, attenuated vaccine within 4 weeks before randomization.
• Radiotherapy within 14 days or focal radiation within 7 days
• Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
• Cytotoxic therapy within 14 days
• PI therapy within 14 days
• IMiD agent therapy within 14 days
• Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
• Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are:

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Janssen Scientific Affairs, LLC: collaborator
• Sarah Cannon: collaborator
• coMMit, Myeloma Trials, Innovated: collaborator

Study Sites (10)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

University of Wisconsin - Carbone

Madison, Wisconsin, 53792, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Luciano Costa, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luciano Costa, MD

CONTACT

205-934-9695; ljcosta@uabmc.edu

Margaret A Thomas, MPH

CONTACT

margaretathomas@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Eligible patients are enrolled in arm M for induction therapy, corresponding to 6 cycles of Dara-VRd. Upon completion of induction, patients undergo MRD assessment by next-generation sequencing utilizing ClonoSEQ® (MRD1) and undergo mobilization and collection of autologous hematopoietic progenitor cells for future AHCT. Upon confirmation of adequate hematopoietic cell collection (≥2 x 10\^6 CD34+ cells/kg) and result of MRD1 patients will undergo randomization according to the MRD-assigned cohort * MRD negative cohort - Patients will be randomized between arm A and arm B for intensification and maintenance. * MRD positive cohort - Patients will be randomized between arm C and arm D for intensification, consolidation and maintenance.

Study Record Dates

• First Submitted: January 29, 2022
• First Posted: February 9, 2022
• Study Start: December 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)