Study of SubQ Dara With Dose-Attenuated Bortezomib, Lenalidomide, Dexamethasone in Elderly NDMM

NCT04052880 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: GCO 19-0944
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, phase 2 study in elderly (age ≥ 70) subjects with newly diagnosed multiple myeloma who are transplant ineligible. Subjects will receive subcutaneous daratumumab, dose-attenuated bortezomib, revlimid, and dexamethasone until confirmed disease progression, discontinuation of study treatment due to unacceptable drug toxicity, or other reasons. Throughout the study, subjects will be monitored closely for adverse events, laboratory abnormalities, and clinical response.

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

Multiple myeloma; Newly diagnosed multiple myeloma; Myeloma; Elderly; Daratumumab

Outcome Measures

Primary Outcomes (1)

• Responses: VGPR or better

  ≥ VGPR rate after 8 cycles of therapy, defined as the proportion of subjects who have achieved VGPR or better, according to the IMWG criteria.

  At the end of cycle 8, each cycle is 28 days

Secondary Outcomes (7)

• Overall Response Rates

  Within a year

• Duration of ORR (≥PR), ≥VGPR, ≥CR, and sCR

  Within two years

• Time to Overall Response Rate

  Within a year

• Time to Progression

  Within 2 years

• Progression Free Survival

  Within 5 years

Study Arms (1)

Daratumumab with dose-attenuated VRd

EXPERIMENTAL

SubQ Daratumumab with Dose-Attenuated VRd

Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Ixazomib

Interventions

Daratumumab DRUG

Daratumumab 1800 mg will be delivered by subcutaneous injection given through a syringe and needle by a manual push over approximately 3 to 5 minutes. Doses will be administered at alternating locations on the abdomen. Daratumumab will be administered weekly during treatment in Cycles 1 to 2, every 2 weeks during cycles 3-6, and every 4 weeks thereafter.

Daratumumab with dose-attenuated VRd

Bortezomib DRUG

Subjects will receive 1.3 mg/m2 bortezomib as a subcutaneous infusion on Days 1, 8, and 15 during the 28-day cycles.

Daratumumab with dose-attenuated VRd

Lenalidomide DRUG

In Cycles 1 through 12, lenalidomide will be self-administered at a dose of 15 mg orally each day on Days 1 through 21 of each 28-day cycle. For subjects with CrCl 30-60mL/min, lenalidomide will be reduced to 10mg daily, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5mg daily. In maintenance phase: lenalidomide will be administered at one dose level below Cycles 1-12 dosing ie 10 mg orally daily. In maintenance, for subjects with CrCl 30-60 mL/min, lenalidomide will be reduced to 5 mg daily during maintenance treatment, and for subjects with CrCl 15-30 mL/min, lenalidomide will be reduced to 5 mg every other day during maintenance treatment.

Daratumumab with dose-attenuated VRd

Dexamethasone DRUG

Dexamethasone will be self-administered orally at a total dose of 20 mg weekly during cycles. However, the dexamethasone 20 mg oral or IV (only if oral is not available) dose administered as a preinfusion medication on daratumumab infusion days replaces the oral dexamethasone dose for that day. Dexamethasone will be administered until the subject experiences disease progression or unacceptable toxicity. In the maintenance phase, dexamethasone/steroid premedications may be tapered or discontinued in the absence of daratumumab related infusion reactions/based on patient tolerance. In the event of persistent daratumumab related infusion reactions, the least amount of steroid premedications needed to prevent the same may be used.

Daratumumab with dose-attenuated VRd

Ixazomib DRUG

During maintenance treatment, if choice of maintenance therapy includes ixazomib, ixazomib will be administered at 3 mg orally daily on Days 1,8, and 15 of each cycle. For subjects with CrCl 15-30 mL/min, ixazomib will be reduced to 2.3 mg once per week during maintenance treatment.

Daratumumab with dose-attenuated VRd

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Newly diagnosed, untreated, symptomatic MM as defined by standard criteria. Clonal bone marrow plasma cells \>10% or biopsy-proven bony or extramedullary plasmacytoma\* and any one or more of the following myeloma-defining events:
• Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium \>0.25 mmol/L (\> 1mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\>11 mg/dL) and/or,
• Renal insufficiency: creatinine clearance \<40 mL per min or serum creatinine \>177 µmol/L (\>2 mg/dL) and/or,
• Anemia: hemoglobin value of \>20 g/L (\>2g/100 mL)below the lower limit of normal, or a hemoglobin value \<100 g/L (10g/100 mL) and/or,
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT (if bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement)
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage\*\* (clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used ≥60% or
• Serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or
• More than one focal lesion on MRI\*\*\* (Each focal lesion must be 5 mm or more in size.
• Age ≥ 70 and ineligible for autologous hematopoietic stem cell transplantation (defined as age, ≥ 80 or age \< 80 with cardiac/pulmonary/ or other comorbidities deemed by investigator likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patients must have measurable disease defined by at least 1 of the following 3 measurements:
• Serum M-protein \> 1 g/dL (10 g/L) or \> 0.5 g/dL if IgA
• Urine M-protein \> 200 mg/24 hours.

You may not qualify if:

• Peripheral neuropathy \> Grade 2 or \>Grade 1 with pain on clinical examination during the Screening period.
• Kidney failure with CrCl ≤ 15 mL/min by Cockfraft Gault
• Significant cardiac disease as determined by the investigator including:
• Known or suspected cardiac amyloidosis
• Congestive heart failure of Class III or IV of the NYHA classification
• Uncontrolled angina, hypertension or arrhythmia
• Myocardial infarction in the past 6 months
• Any uncontrolled or severe cardiovascular disease
• QTc \> 470 milliseconds (msec) on a 12-lead ECG obtained during the Screening period. If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG or by manual calculation.
• Prior cerebrovascular event with persistent neurologic deficit.
• Subject is:
• 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 realtime 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).
• Human immunodeficiency virus infection
• Any medical conditions that, in the investigator's opinion, would impose excessive risk to the subject.

Sponsors & Collaborators

• Larysa Sanchez: lead
• Janssen, LP: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; ixazomib

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)

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

Study Officials

• Larysa Sanchez

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Sundar Jagannath, MBBS

  Icahn School of Medicine at Mount Sinai

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: All subjects will receive initial therapy with 12 cycles of daratumumab in combination with dose-attenuated bortezomib, lenalidomide and dexamethasone (VRd). Maintenance treatment cycles are 28 days in duration with daratumumab and either lenalidomide or ixazomib. The choice of maintenance therapy will be based on cytogenetic risk status at diagnosis. For patients with high-risk MM defined by FISH with t(4;14) only; maintenance therapy will consist of daratumumab with ixazomib. For all other patients, maintenance therapy will consist of daratumumab with lenalidomide. All subjects will continue maintenance treatment until disease progression, except maintenance daratumumab will be discontinued after 2 years if subjects remain on maintenance treatment at that time.

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 12, 2019
• Study Start: October 24, 2019
• Primary Completion: May 20, 2025
• Study Completion: May 1, 2026
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)