Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

NCT04151667 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: MCC-20130
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II study of daratumumab based therapies for older adults with multiple myeloma.

Conditions

Multiple Myeloma

Keywords

myeloma; daratumumab

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall Response Rate of the response adapted strategy using the uniform response criteria of the International Myeloma Working Group (IMWG). Stringent Complete Response (sCR): Below plus normal FLC ratio and absence of clonal cells in bone marrow3 by immunohistochemistry or immunofluorescence Complete Response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or \> 90% reduction in serum M-protein plus urine M-protein level \< 100 mg/24 h Partial Response (PR): \> 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>90% or to \< 200 mg/24 h Minimal Response (MR): 25%-49% reduction of serum M-protein and 50%-89% reduction in 24 hours urinary M-protein Stable Disease (SD): Not meeting criteria for sCR, CR, VGPR, PR, MR, or Progressive Disease (PD)

  Up to 8 months

Secondary Outcomes (2)

• Progression Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

Other Outcomes (2)

• Number of Participants Who Continue on Arm A After 2 Cycles

  At the end of Cycle 2 (each cycle is 28 days)

• Number of Participants Without Minimal Residual Disease

  Up to 8 months

Study Arms (3)

A: Daratumumab & Dexamethasone

EXPERIMENTAL

All participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.

Drug: Daratumumab Injection; Drug: Dexamethasone Oral

B: Daratumumab, Dexamethasone and Lenalidomide

EXPERIMENTAL

Participants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.

Drug: Daratumumab Injection; Drug: Dexamethasone Oral; Drug: Lenalidomide Pill

C: Daratumumab, Dexamethasone and Bortezomib

EXPERIMENTAL

Participants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m\^2 Days 1,8 and 15 of each 28 day treatment cycle.

Drug: Daratumumab Injection; Drug: Dexamethasone Oral; Drug: Bortezomib Injection

Interventions

Daratumumab Injection DRUG

Patient will receive daratumumab (1800 mg in 15 ml) administered by manual subcutaneous injections weekly for the first 8 weeks, every other week for the next 16 weeks and every 4 weeks after.

Also known as: Darzalex

A: Daratumumab & Dexamethasone; B: Daratumumab, Dexamethasone and Lenalidomide; C: Daratumumab, Dexamethasone and Bortezomib

Dexamethasone Oral DRUG

The dexamethasone starting dose will be 20 mg PO once a week. Commercial dexamethasone will be used. Dexamethasone is often supplied in 4 mg tablets. Accordingly, patients will take 5 (4 mg tablets) one day of the week prior to the administration of daratumumab if this corresponds to a daratumumab dosing days. In non daratumumab dosing days, dexamethasone will be taken by the patient at home, usually in the morning with breakfast.

Also known as: Decadron

A: Daratumumab & Dexamethasone; B: Daratumumab, Dexamethasone and Lenalidomide; C: Daratumumab, Dexamethasone and Bortezomib

Bortezomib Injection DRUG

Bortezomib will be given weekly subcutaneously in an effort to decrease the toxicity of the therapy. Specifically patients will receive a starting dose of bortezomib of 1.3 mg/m\^2 Days 1,8,15 of a 28 day cycle. Bortezomib will be administered in the cancer center per standard of care procedures.

Also known as: Velcade

C: Daratumumab, Dexamethasone and Bortezomib

Lenalidomide Pill DRUG

Lenalidomide will be given orally on days 1-21 of a 28 days cycle. The starting dose of lenalidomide will be based on the patient creatinine clearance per the package insert. Specifically patients with a creatinine clearance ≥ 50 ml/min will receive 25 mg of lenalidomide PO Days 1-21. Patients with a creatinine clearance ≥ 30 but less than 50 ml/min will receive 10 mg of lenalidomide. Patients with a creatinine clearance \< 30 ml/min are not eligible but patients who experience a deterioration in the renal function during screening or treatment may continue on lenalidomide therapy as long as the risk / benefit profile is deemed acceptable, that study therapy is in the best interest of the patient and after discussion with the study principal investigator / sponsor.

Also known as: Revlimid

B: Daratumumab, Dexamethasone and Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent form
• Age 65 years or older and presence of coexisting conditions which in the opinion of the treating physician are likely to result in the development of unacceptable side effects associated with high-dose chemotherapy with stem-cell transplantation
• Able to adhere to the study visit schedule and other protocol requirements.
• Diagnosed with multiple myeloma and be considered to have active disease with either elevated Calcium, Renal Failure, Anemia, Bone Lesions (CRAB) criteria (hypercalcemia, renal failure, anemia, or bone lesions) or myeloma defining events (bone marrow ≥ 60% plasma cells, serum free light chain (sFLC) ratio≥ 100 or MRI or Positron Emission Tomography \[PET\] defined lesions). Patients must not have received an active chemotherapy regimen. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start. Dexamethasone up to 160 mg total dose is allowed prior to participation
• Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100mg/L)
• Eastern Cooperative Group (ECOG) Performance Status of 0 - 2.
• Serum bilirubin levels \</=1.5 times the upper limit of the normal range for the laboratory (ULN).
• Serum Aspirtate Transaminase (AST) or serum Alanine Aminotransferase (ALT) levels \</=2 x Upper Limit of Normal (ULN)
• Must have adequate bone marrow function: a. Absolute neutrophil count \> 1,000 cells/mm3 (1.0 x 109/L). b. Platelets \>/= 75,000 /mm3.
• Hemoglobin \> 8 g/dL (transfusions are allowed)
• Calculated creatinine clearance \>/=30ml/min by Cockcroft-Gault formula.
• Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

You may not qualify if:

• Ongoing severe infection requiring intravenous antibiotic treatment.
• Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years.
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Patients with known Chronic Obstructive Pulmonary Disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal and , moderate or severe persistent asthma within the past 2 years or uncontrolled asthma. Patients with a history of COPD will have pulmonary function testing to include FEV1
• Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or lactating females.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Concurrent use of other anti-cancer agents or treatments with the exception for hormonal therapy, which is allowed.
• Known allergy or hypersensitivity or intolerance to any of the study drugs, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients (refer to daratumumab IB), or known sensitivity to mammalian derived products
• Seropositive for human immunodeficiency virus (HIV)
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Seropositive for hepatitis C (except in the setting of a Sustained Virologic Response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

H. Lee Moffitt Cancer & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Meads MB, Zhao X, Noyes D, Sudalagunta PR, Achille A, Zhang C, Canevarolo RR, Silva M, Magaletti D, DeAvila D, Toska S, Oates A, Lastorino D, Idiaquez DW, Song J, Sansil SS, Yoder SJ, Grajales-Cruz AF, Blue B, Freeman CL, Kim J, Alsina M, Brayer J, Silva AS, Song X, Shain KH, Baz R. Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy. Blood. 2026 Jan 29;147(5):497-512. doi: 10.1182/blood.2025029921.

  PMID: 40983035 DERIVED

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

daratumumab; Dexamethasone; Calcium Dobesilate; Lenalidomide; Bortezomib

Condition Hierarchy (Ancestors)

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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Results Point of Contact

• Title: Dr. Rachid Baz
• Organization: Moffitt Cancer Center

Rachid.Baz@moffitt.org

813-745-3163

Study Officials

• Rachid C Baz, MD

  H. Lee Moffitt Cancer & Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: November 22, 2019
• Primary Completion: November 8, 2023
• Study Completion: May 7, 2026
• Last Updated: March 11, 2026
• Results First Posted: December 30, 2024

Record last verified: 2026-02

Locations

US (1)