Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma

NCT03697655 | Unknown Phase 2

• 1 other identifier: PMC008
• Study Type: interventional
• Target: 274
• Locations: 1 country
• Sites: 2

Brief Summary

PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (ESF)

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

  from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks

Secondary Outcomes (2)

• Overall Response Rate

  from randomization till progression or death from any cause, up to 129 weeks

• Overall Survival

  throughout the duration of the study, no longer than 6 years

Study Arms (4)

PREDATOR-BR Cohort A

EXPERIMENTAL

n=46, Daratumumab 20 MG/ML \[Darzalex\], 16 mg/kg body weight administered as an intravenous infusion

Drug: Daratumumab 20 MG/ML [Darzalex]

PREDATOR-BR Cohort B

NO INTERVENTION

n=46, Control Group, Observation (no treatment)

PREDATOR-MRD Cohort A

EXPERIMENTAL

n=59, Daratumumab 20 MG/ML \[Darzalex\], 16 mg/kg body weight administered as an intravenous infusion

Drug: Daratumumab 20 MG/ML [Darzalex]

PREDATOR-MRD Cohort B

NO INTERVENTION

n=59, Control Group, Observation (no treatment)

Interventions

Daratumumab 20 MG/ML [Darzalex] DRUG

Daratumumab dose 16 mg/kg body weight to be administered as an IV infusion. treatment given until clinical progression or SPR but no longer than 73 weeks

Also known as: Darzalex

PREDATOR-BR Cohort A; PREDATOR-MRD Cohort A

Eligibility Criteria

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

You may qualify if:

• 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.
• Males and females ≥18 years of age.
• Life expectancy of more than 3 months.
• ECOG performance status of 0-2.
• Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
• ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
• 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.
• 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.
• FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
• 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.
• Voluntary written informed consent.

You may not qualify if:

• Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria.
• 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, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by \< 2 months.
• Patients who have already started or received post-transplant maintenance or consolidation treatment.
• Subject has received daratumumab or other anti-CD38 therapies previously.
• Patients not able to tolerate daratumumab or required concomitant medication and procedures.
• 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.
• 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).
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Plasma cell leukemia.
• Waldenström's macroglobulinemia.
• CNS involvement.
• Pregnant or lactating females.
• Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
• Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
• 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.

Sponsors & Collaborators

• Polish Myeloma Consortium: lead
• Janssen-Cilag Ltd.: collaborator
• Bioscience, S.A.: collaborator

Study Sites (2)

Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku

Poznan, Greater Poland Voivodeship, 60-569, Poland

RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, 02-776, Poland

RECRUITING

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

• Krzysztof Jamroziak, MD, PhD

  Polish Myeloma Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Krzysztof Jamroziak, MD, PhD

CONTACT

+48 504 065 262; k.m.jamroziak@gmail.com

Dominik Dytfeld, MD, PhD

CONTACT

+48 602 464 708; dytfeld@me.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: treatment arm and control (observation) arm

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: October 5, 2018
• Study Start: December 10, 2018
• Primary Completion: September 1, 2020
• Study Completion: July 1, 2024
• Last Updated: January 3, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (2)