Clinical Trial conduct to investigate if Daratumumab therapy for multiple myeloma patients with minimal residual disease (MRD) reappearance or biochemical relapse is effective in preventive therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Polish Myeloma Consortium

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Nov 2018 → 26 Nov 2025

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

JANSSEN PHARMACEUTICALS

External identifiers

EU CT number

2024-518400-50-00

EudraCT number

2017-003253-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy, Therapy

PREDATOR-BR: To compare EFS between daratumumab arm and observation arm after randomization of patients with biochemical relapse of MM. EFS is defined as the time from randomization date to the date of development of new CRAB symptom(s), SPR or death from any cause.
PREDATOR-MRD: To compare event-free survival (EFS) between daratumumab arm and observation arm after randomization of patients with reappearance of MRD in MM. EFS is defined as the time from randomization date to the date of development of new CRAB symptom(s), SPR or death from any cause.

Secondary objectives 11

1. PREDATOR-BR To assess the efficacy of daratumumab treatment in MM patients who experienced a biochemical relapse
2. PREDATOR-BR: To determine time to MRD negativity
3. PREDATOR-BR/ MRD: To determine the rate of MRD negative disease at completion of treatment with daratumumab (at 19 months)
4. PREDATOR-BR:To evaluate the safety and tolerability of daratumumab in MM patients with biochemical relapse
5. PREDATOR-BR/ MRD: To evaluate and compare changes in quality of life (QOL) of subjects in the daratumumab therapy cohort with those in the observation cohort
6. PREDATOR-BR/ MRD: To evaluate and compare changes in quality of Life (QOL) of patients treated with daratumumab iv and those treated with daratumumab sc
7. PREDATOR-BR/ MRD: To compare overall survival between arms
8. PREDATOR-MRD: To assess the efficacy of daratumumab treatment in MM patients who experienced MRD reappearance.
9. PREDATOR-MRD: To assess the time to MRD negativity achievement on treatment with daratumumab.
10. PREDATOR-MRD: To assess the time from MRD reappearance to clinical progression or SPR in observation arm.
11. PREDATOR-MRD: To evaluate the safety and tolerability of daratumumab in MM patients with MRD reappearance.

Conditions and MedDRA coding

Multiple Myeloma and Minimal Residual Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. PREDATOR-BR: Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved at least PR to last line of therapy, and who experience asymptomatic biochemical progression not meeting criteria for SPR.
2. Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
3. Voluntary written informed consent.
4. Males and females ≥18 years of age.
5. Life expectancy of more than 3 months.
6. ECOG performance status of 0-2.
7. Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
8. ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
9. Calculated creatinine clearance (by Cockroft-Gault) ≥50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 – age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL.
10. Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential.
11. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
12. PREDATOR-MRD: Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved CR with negative MRD to the last line of therapy, and a. remain in CR MRD negative based on MRD flow cytometry assessment at screening (repeating MRD evaluation is not needed if CR MRD negative status in bone marrow sample using flow cytometry with sensitivity of at least 10-5 was confirmed not earlier than 3 months before inclusion to the study) or b. have CR with positive flow cytometry MRD status based on MRD flow cytometry assessment at screening. Those patients will be randomized directly after screening without entering MRD observation phase.

Exclusion criteria 21

1. Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria.
2. Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h in two consecutive measurements separated by < 2 months, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
3. Subject has received daratumumab or other anti-CD38 therapies previously.
4. Patients not able to tolerate daratumumab or required concomitant medication and procedures.
5. 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 <50% of predicted normal.
6. Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, 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).
7. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
8. Plasma cell leukemia.
9. Waldenström’s macroglobulinemia.
10. CNS involvement.
11. Pregnant or lactating females.
12. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
13. Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
14. Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
15. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening.
16. Patient who in investigator’s opinion is unable to comply with the protocol requirements.
17. Uncontrolled hypertension or diabetes.
18. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study.
19. Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
20. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone.
21. Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To compare (EFS) between daratumumab arm and observation arm after randomization of patients with biochemical relapse of MM. To compare (EFS) between daratumumab arm and observation arm after randomization of patients with reappearance of MRD in MM.

Secondary endpoints 1

1. SPR, CRAB or death. Overall response rate (ORR) as determined by Investigator evaluation, defined as the percentage of subjects achieving an objective response (i.e., partial response or better), using the IMWG Consensus Panel 1 response criteria.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Polish Myeloma Consortium

Sponsor organisation

Polish Myeloma Consortium

Address

Ul. Augustyna Szamarzewskiego 84

City

Poznan

Postcode

60-569

Country

Poland

Scientific contact point

Organisation

Polish Myeloma Consortium

Contact name

President

Public contact point

Organisation

Polish Myeloma Consortium

Contact name

Clinical Trial Information Desk

Third parties 1

Locations

1 EU/EEA country · 7 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