Efficacy of Daratumumab in Patients With Relapsed/Refractory Myeloma With Renal Impairment

NCT03450057 | Completed Phase 2 Results

• 2 other identifiers: EAE-2017/MM022017-003950-18
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to evaluate the effects of daratumumab with dexamethasone (DaraD) in subjects with relapsed or refractory multiple myeloma and renal impairment.

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

Multiple Myeloma; MM; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• The Evaluation of Progression Free Survival (PFS) in Subjects With Relapsed or Refractory Multiple Myeloma and Renal Impairment Treated With Daratumumab and Dexamethasone.

  Progression free survival was defined as the time, in months, from treatment initiation (C1D1) to the date of the first documented disease progression or death due to any cause, whichever came first. Clinical deterioration was not considered progression. For patients who neither progressed nor died, the survival time was censored at the date of their last disease assessment. For patients who started a new anti-tumor treatment, survival time was censored at the date of the start of the new treatment.

  Duration from first daratumumab administration until death or last assessment, months.

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months)

• Renal Response Rate (RRR)

  From first dose of Daratumumab until end of treatment, PD or death (approximately up to 30 months )

• Duration of Response in Patients With RI

  Assessed monthly from first dose of Daratumumab until PD or death from any cause (approximately up to 30 months)

• Time to Next Therapy

  From first dose until the date to next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 30 months)

• Overall Survival

  Time from first dose of study treatment to death (approximately up to 30 months)

Study Arms (1)

Single arm trial receiving daratumumab with dexamethasone (DaraD)

EXPERIMENTAL

Daratumumab was given at a dose of 16 mg/kg administered as an intravenous (IV) infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Dexamethasone was administered according to the standard recommended dose of 40 mg (20 mg for patients \> 75 years of age) orally once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Drug: Daratumumab with dexamethasone

Interventions

Daratumumab with dexamethasone DRUG

Daratumumab: Daratumumab was given at a dose of 16 mg/kg administered as an intravenous (IV) infusion at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter. Subjects received pre-infusion medications before infusions to mitigate potential infused-related reactions (IRRs). Dexamethasone: Dexamethasone was administered at 40 mg (20 mg for patients \>75 years of age) orally, once daily on Days 1, 8, 15, and 22 of each 28-day treatment cycle.

Also known as: DaraD, Darzalex, Dara, Dex

Single arm trial receiving daratumumab with dexamethasone (DaraD)

Eligibility Criteria

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

You may qualify if:

• Males and females at least 18 years of age.
• Voluntary written informed consent before performance of any study-related procedure.
• Subject must have documented multiple myeloma as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma.
• AND any 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:
• Hypercalcaemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11 mg/dL)
• Renal insufficiency: creatinine clearance \<40 mL per min or serum creatinine \>177 μmol/L (\>2 mg/dL)
• Anaemia: haemoglobin value of \>20 g/L below the lower limit of normal, or a haemoglobin value \<100 g/L
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PETCT
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage ≥60%
• Involved:uninvolved serum free light chain ratio ≥100
• \>1 focal lesions on MRI studies
• Prior treatment with at least two lines of treatment that included both bortezomib- and lenalidomide based regimens.

You may not qualify if:

• Previous therapy with daratumumab or other anti-CD38 therapy.
• Anti-myeloma treatment within 2 weeks prior to Cycle 1, Day 1.
• Cumulative dose of corticosteroids greater than or equal to the equivalent of 140mg prednisone for ≥ 4 days or a dose of corticosteroids greater than or equal to the equivalent of 40 mg/day of dexamethasone for ≥ 4 days within the 2-week period prior to Cycle 1, Day 1.
• Previous allogenic stem cell transplant; or Autologous Stem Cell Transplantation (ASCT) within 12 weeks before Cycle 1, Day 1.
• Clinical signs of meningeal involvement of multiple myeloma.
• Subject has either of the following:
• Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 \<50% of predicted normal.
• Known moderate or severe persistent asthma (see Appendix 7), within 2 years from C1D1, or currently has uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
• Clinically significant cardiac disease, including:
• Myocardial infarction within 1 year, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV).
• Uncontrolled cardiac arrhythmia (CTCAE Grade 2 or higher) (atrial fibrillation with controlled ventricular rate is allowed) or clinically significant ECG abnormalities.
• ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec.
• Any of the following:
• Known active hepatitis A
• Patient 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 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.

Sponsors & Collaborators

• Hellenic Society of Hematology: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

General Hospital of Athens "Alexandra"

Athens, Attica, 11528, Greece

Location

Related Publications (1)

• Kastritis E, Terpos E, Symeonidis A, Labropoulou V, Delimpasi S, Mancuso K, Zamagni E, Katodritou E, Rivolti E, Kyrtsonis MC, Roussou M, Fotiou D, Theodorakakou F, Ntanasis-Stathopoulos I, Hatjiharissi E, Kanellias N, Migkou M, Cheliotis G, Manousou K, Gavriatopoulou M, Dimopoulos MA. Prospective phase 2 trial of daratumumab with dexamethasone in patients with relapsed/refractory multiple myeloma and severe renal impairment or on dialysis: The DARE study. Am J Hematol. 2023 Sep;98(9):E226-E229. doi: 10.1002/ajh.27001. Epub 2023 Jun 21. No abstract available.

  PMID: 37340832 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

daratumumab; Dexamethasone; darlin protein, Dictyostelium

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

None reported.

Results Point of Contact

• Title: Prof. Evangelos Terpos
• Organization: General Hospital of Athens 'Alexandra', Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine

eterpos@med.uoa.gr

+302102162540

Study Officials

• Efstathios Kastritis, Assoc Prof

  National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Model Details: Single arm: Daratumumab and Dexamethasone

Study Record Dates

• First Submitted: February 13, 2018
• First Posted: March 1, 2018
• Study Start: February 15, 2018
• Primary Completion: March 22, 2021
• Study Completion: March 22, 2021
• Last Updated: March 29, 2024
• Results First Posted: August 28, 2023

Record last verified: 2022-10

Locations

GR (1)