Daratumumab in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma and Severe Renal Impairment

NCT02977494 | Completed Phase 2 DMC

• 1 other identifier: 2016-000433-51
• Study Type: interventional
• Target: 22
• Locations: 2 countries
• Sites: 10

Brief Summary

Myeloma patients with renal impairment need a rapid and effective reduction of tumor burden to enable renal recovery, which is correlated with prognosis of the patients. However, effective combination regimens are often hampered by necessary dose reductions or increased toxicity in renally impaired patients. The well known positive effects on renal impairment by Bortezomib combined with Daratumumab, which, as all monoclonal Antibody, is not renally excreted or metabolized and as so far known should not add significant toxicity but efficacy, makes the proposed combination of Daratumumab, Bortezomib and Dexamethasone highly attractive for renally impaired MM patients. In the current clinical trials with Daratumumab patients with renal function impairment (GFR ≤ 20 ml/min) were so far excluded. Consequently questions about efficacy, safety and pharmacokinetics of Daratumumab in combination with Bortezomib and Dexamethasone in patients with relapsed and refractory MM and severe renal impairment are still unanswered. This trial will answer these questions for a patient group, who has still an unmet need for novel and effective treatment options

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Evaluate the efficacy (overall response rate, ORR according to IMWG recommendations) of the combination of daratumumab, bortezomib and dexamethasone in subjects with relapsed and refractory MM and impaired renal function

  two years

Study Arms (1)

Daratumumab Bortezomib

EXPERIMENTAL

Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab (JNJ-54767414) is a novel human IgG1monoclonal Antibody (mAb) that binds with high affinity to a unique epitope on CD38

Also known as: Darzalex

Daratumumab Bortezomib

Bortezomib DRUG

Also known as: Velcade

Daratumumab Bortezomib

Dexamethasone DRUG

Also known as: Fortecortin

Daratumumab Bortezomib

Eligibility Criteria

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

You may qualify if:

• Subjects must be at least 18 years of age
• Written informed consent
• Subjects must have had documented multiple myeloma requiring treatment as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow \> 10% and/or presence of a biopsy-proven plasmacytoma at some point in their disease history requiring treatment according diagnostic criteria (IMWG updated criteria 2014, Rajkumar et al. 2014) see appendix I With measurable disease at screening (serum M-protein \> 500 mg/dl or urine M-protein \> 200 mg/24h, in case of oligosecretory MM serum free light chain \> 10 mg/dl and abnormal kappa/lambda free light chain ratio)
• GFR \< 30 ml/min and /or subjects undergoing hemodialysis
• Subject must have received at least 1 prior treatment line
• Subjects must have documented evidence of progressive disease after the last treatment line
• ECOG performance status 0-3 (ECOG 3 is only allowed if due to myeloma disease)
• Subjects must have certain pretreatment laboratory values meeting the following criteria during the Screening Phase:
• Hemoglobin ≥7.5 g/dl (4,66 mmol/L; prior red blood cells (RBC) transfusion or recombinant human erythropoietin use is permitted).
• Absolute neutrophil count ≥ 1.0 x109/L (granulocyte colony stimulating factor (GCSF) use is permitted);
• Platelet count more or equal 70 x109/L for subjects in whom ˂ 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count ˃ 50 x 109/L (transfusions are not permitted to achieve this minimum platelet count ),
• Aspartate aminotransferase (AST) ≤ 2,5 x upper limit of normal (ULN);
• Alanine aminotransferase (ALT) ≤ 2,5 x ULN
• Total bilirubin ≤ 2.0 x ULN ,except in subjects with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin ≤ 2.0 x ULN

You may not qualify if:

• Subject has received prior Daratumumab or other Anti-CD38 antibodies (previous treatment with Elotuzumab is allowed)
• Evidence of intolerance to bortezomib or known allergies, hypersensitivity or intolerance to monoclonal antibodies
• Subject has received anti-myeloma treatment within 2 weeks of Cycle 1, day 1. The only exception is emergency use of a short course of corticosteroids (equivalent of Dexamethasone 40 mg/day for a maximum of 4 days) before treatment.
• Active graft-versus host disease under immunosuppressive treatment
• Subject is a woman who is pregnant or breastfeeding
• Active, uncontrolled infection.
• Subject has peripheral neuropathy ≥ 3 or neuropathic pain Grade 2 or higher
• Subject has either of the following:
• Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is only required for subjects suspected of having COPD
• Known moderate or severe persistent asthma, 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).
• Subject has clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry, unstable angina, cardiac insufficiency New York Heart Association (NYHA) Class III-IV or uncontrolled arrhythmia
• Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significant is defined by presence of serum M-protein ˂ 3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less (Kyle et al. 2003). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment and organ damage (Kyle et al., 2003, 2007).
• Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Subject has had radiation therapy within 14 days of treatment
• Subject has had plasmapheresis within 14 days of treatment. Screening laboratory values have to be performed after end of plasmapheresis.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (10)

Charité Universitätsmedizin BerlinCampus Benjamin Franklin

Berlin, Germany

Location

Vivantes Klinikum Neukölln

Berlin, Germany

Location

Klinikum Chemnitz GmbH

Chemnitz, Germany

Location

Katholische Karl-Leisner Klinikum Goch

Goch, Germany

Location

Asklepios Klinik Altona

Hamburg, Germany

Location

University Hospital Hamburg Eppendorf

Hamburg, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Univerisity Hospital Muenster

Münster, Germany

Location

University Hospital

Tübingen, Germany

Location

Alexandra Hopsital

Athens, Greece

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Dexamethasone; dexamethasone acetate

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

Study Design

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

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 30, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: May 31, 2022

Record last verified: 2022-05

Locations

GR (1); DE (9)