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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cologne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

31 May 2021 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Janssen-Cilag

External identifiers

EU CT number

2024-517761-17-00

EudraCT number

2019-003856-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The aim of the trial is to investigate the safety and efficacy of daratumumab added to a standard induction regimen of bortezomib, cyclophosphamide and dexamethasone (VCd).

Secondary objectives 6

1. Assess the efficacy of induction and maintenance therapy using daratumumab in combination with bortezomib and dexamethasone by evaluating MRD negativity before and during the maintenance therapy.
2. Evaluate the response and progression-free survival of a daratumumab-containing regimen at first progression/relapse 12 months after start of second line therapy.
3. Assess the progression-free survival (PFS) of first line therapy.
4. Evaluate time to next treatment (TTNT) of first line therapy DVCd.
5. Examine overall survival (OS) at the timepoint of 36 months after start of second line treatment.
6. Investigate the overall response rate to first- and second-line treatment using the IMWG response criteria.

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Signed Written Informed Consent
2. Untreated patients with multiple myeloma diagnosis according to the International myeloma working group (IMWG) diagnostic criteria
3. ECOG ≤2
4. Not eligible or willing for autologous transplantation
5. Age 18 years or above
6. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception and must agree to use adequate method to avoid pregnancy for 6 months after the last dose of IMP.
7. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25IU/L or equivalent units of β-HCG) within one to two weeks prior to the start of Daratumumab
8. Women will be not be considered to be of childbearing potential if they are post-menopausal and/or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). To be considered post-menopausal the appropriate age-specific requirements have to be met.
9. Women must not be breastfeeding.
10. Male trial participants who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year and must be willing to adhere to any approved contraception method for a period of 6 months post treatment completion.

Exclusion criteria 23

1. Subject has received any multiple myeloma therapy previously, except dexamethasone to a maximum cumulative dose of 160mg, emergency radiotherapy or surgery for symptom control
2. Participation in other interventional clinical trials
3. Subject has known meningeal involvement of multiple myeloma.
4. Subjects with plasma cell leukemia or AL amyloidosis
5. Non-hematologic malignancy within the past 2 years with the exception defined in the protocol
6. 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.
7. 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 trial.
8. Subject is known to be seropositive for human immunodeficiency virus (HIV)
9. Active hepatitis B (defined by a positive test for HBV DNA) or hepatitis C (defined by a positive test for HCV-RNA-quantification). (Patients with a positive test for HBs antigen or antibodies, but negative HBC DNA may be included but must be monitored for HBV activation throughout the study.)
10. Subject has any concurrent medical condition or disease (e.g. active systemic infection) that is likely to interfere with trial procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this trial.
11. Concomitant chemotherapy or myeloma-specific therapy other than trial treatment (incl. standard intensification) is not permitted. The sponsor must be notified in advance (or as soon as possible thereafter) of any instances on which prohibited medications are administered.
12. Patients has known current symptomatic congestive heart failure (New York Heart Association Class III-IV, see APPENDIX III B) unstable angina pectoris, or uncontrolled cardiac arrythmia
13. Absolute neutrophil count ≤0.5 × 109/L
14. Platelet count <30 × 109/L
15. Aspartate aminotransferase (AST) or alanine aminotransferase level (ALT) ≥4.5 times the upper limit of normal (ULN)
16. Alkaline phosphatase level ≥4.5 × ULN
17. Total bilirubin level ≥2.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 1.5 × ULN)
18. Pregnant women and nursing mothers, or women planning to become pregnant while enrolled in this trial or within 3 months after the last dose of daratumumab
19. Failure to use highly-effective contraceptive methods.
20. Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator
21. Legally incapacitated persons
22. Subject is known or suspected of not being able to comply with the trial protocol (e.g. because of alcoholism, drug dependency, or psychological disorder) or the subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g. compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments.
23. Persons held in an institution by legal or official order

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response (≥VGPR) after 8 cycles of DVCd

Secondary endpoints 8

1. Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at a level of 10e-5
2. Progression-free survival at 12 months from start of second line therapy
3. Progression-free survival from trial inclusion (PFS)
4. Time to next treatment (TTNT)
5. Overall survival (OS)
6. Overall response rate of first line treatment
7. Overall response rate of second line treatment
8. Minimal residual disease (MRD) negativity at any time before and during maintenance therapy (DVd) assessed by NGS at other thresholds or by Flow

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cologne

Sponsor organisation

University Of Cologne

Address

Albertus-Magnus-Platz 1

City

Cologne

Postcode

50923

Country

Germany

Scientific contact point

Organisation

University Of Cologne

Contact name

Dr. T. Richardson

Public contact point

Organisation

University Of Cologne

Contact name

DADA Studienzentrale

Third parties 2

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications