Daratumumab for First Line Treatment of Transplant-ineligible Myeloma Patients Followed by Daratumumab Re-treatment at First Relapse

NCT04656951 | Active Not Recruiting Phase 2

• 1 other identifier: Uni-Koeln-3946
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

Daratumumab for first line treatment of transplant-ineligible myeloma patients followed by daratumumab re-treatment at first relapse (GMMG-DADA)

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Efficacy of induction therapy with daratumumab, bortezomib, cyclophosphamide and dexamethasone (DVCd)

  Proportion of patients achieving a very good partial remission (VGPR) or better after 8 cycles of DVCd

  24 weeks

Secondary Outcomes (2)

• Assessment of the efficacy of maintenance therapy until progression using daratumumab in combination with bortezomib and dexamethasone.

  open

• Assessment of the efficacy of a daratumumab-containing regimen at first relapse, following a daratumumab-containing first line regimen.

  up to 48 months (from first progression/relapse until second progression/relapse or death, whichever occurs first (PFS-R)

Study Arms (1)

Daratumumab added to VCd in induction, Vd in maintenance and Rd at relapse

EXPERIMENTAL

Daratumumab at standard dose of 1800 mg will be administered subcutaneously at weekly intervals in cycles 1-2 and every 2 weeks in cycles 3-6 and every 4 weeks in cycles 7-8 together with VCD using bortezomib weekly s.c. for 8 cycles of 28 days each, cyclophosphamide i.v. at 500 mg/m2 on d1 of every cycle and dexamethasone p.o. at 20 mg per week. Maintenance will be daratumumab subcutaneously every 4 weeks with bortezomib s.c. and dexamethasone 20 mg every 2 weeks until progression or intolerance. At relapse/progression treatment will be daratumumab 1800 mg subcutaneously weekly during cycle 1-2, every 2 weeks in cycle 3-6 and every 4 weeks thereafter together with lenalidomide 25 mg p.o. day 1-21 and dexamethasone 20-40 mg weekly.

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab added to induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCD), to bortezomib and dexamethasone during maintenance and to lenalidomide and dexamethasone at progression/relapse.

Also known as: Darzalex

Daratumumab added to VCd in induction, Vd in maintenance and Rd at relapse

Eligibility Criteria

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

You may qualify if:

• Signed Written Informed Consent 1.1 Study participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal study participant care.
• Study participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study.
• Target Population 2.1. Untreated patients with multiple myeloma diagnosis to the IMWG diagnostic criteria 2.2. Subject must have documented multiple myeloma as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow ≥10% at some point in their disease history or presence of a biopsy proven plasmacytoma.
• Measurable disease as defined by any of the following:
• IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
• IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
• Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum Immunoglobulin kappa lambda free light chain ratio.
• ECOG ≤2
• Not eligible for autologous transplantation
• Age 18 years or above
• Reproductive Status
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 5 months (30 days plus the time required for durvalumab to undergo five half-lives) after the last dose of study drug.
• Appropriate methods of contraception are:
• female sterilization or tubal ligation (at least 6 weeks prior to the start of the study treatment),

You may not qualify if:

• Subject has received any multiple myeloma therapy previously except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control
• Participation in other interventional clinial trials
• Subject has known meningeal involvement of multiple myeloma.
• Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of Screening.
• 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 required for subjects suspected of having COPD and subjects must be excluded if FEV1 is \<50% of predicted normal.
• Known moderate or severe persistent asthma, within the past 2 years, 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.
• Use of drugs with significant interaction with or intolerance to the investigational product
• Subject is known to be seropositive for human immunodeficiency virus (HIV)
• active hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\] or positive HBV DNA)
• Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
• Patients has known current symptomatic congestive heart failure (New York Heart Association Class III-IV), unstable angina pectoris, or cardiac arrhythmia
• Subject has any of the following laboratory test results during the Screening Phase:
• Absolute neutrophil count ≤1.0 × 109/L;
• Platelet count \<50 × 109/L

Sponsors & Collaborators

• University of Cologne: lead
• Janssen-Cilag G.m.b.H: collaborator

Study Sites (1)

University of Cologne

Cologne, 50937, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab

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

Study Officials

• Christof Scheid, Prof. Dr.

  University of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 26, 2020
• First Posted: December 7, 2020
• Study Start: June 1, 2021
• Primary Completion: March 15, 2025
• Study Completion (Estimated): December 1, 2031
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)