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

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ClinicalTrials.gov Identifier: NCT03697655
Recruitment Status : Recruiting
First Posted : October 5, 2018
Last Update Posted : January 3, 2019
Sponsor:
Collaborators:
Janssen-Cilag Ltd.
Bioscience, S.A.
Information provided by (Responsible Party):
Polish Myeloma Consortium

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab 20 MG/ML [Darzalex] Phase 2

Detailed Description:

The study is composed of two phase 2 randomized multi-center substudies:

  • PREDATOR-BR: to investigate the role of daratumumab in the setting of biochemical relapse
  • PREDATOR-MRD: to investigate the role of daratumumab in minimal residual disease (MRD) reappearance

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 274 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: treatment arm and control (observation) arm
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR)
Actual Study Start Date : December 10, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: PREDATOR-BR Cohort A
n=46, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion
Drug: Daratumumab 20 MG/ML [Darzalex]
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
Other Name: Darzalex

No Intervention: PREDATOR-BR Cohort B
n=46, Control Group, Observation (no treatment)
Experimental: PREDATOR-MRD Cohort A
n=59, Daratumumab 20 MG/ML [Darzalex], 16 mg/kg body weight administered as an intravenous infusion
Drug: Daratumumab 20 MG/ML [Darzalex]
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
Other Name: Darzalex

No Intervention: PREDATOR-MRD Cohort B
n=59, Control Group, Observation (no treatment)



Primary Outcome Measures :
  1. Event Free Survival (ESF) [ Time Frame: from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks ]
    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


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: from randomization till progression or death from any cause, up to 129 weeks ]
    ORR as determined by Investigator evaluation, defined as the percentage of subjects achieving an objective response (i.e. partial response or better), using IMWG Consensus Panel 1 response criteria

  2. Overall Survival [ Time Frame: throughout the duration of the study, no longer than 6 years ]
    To compare overall survival between arms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

PREDATOR-BR:

Inclusion Criteria:

  1. 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. Males and females ≥18 years of age.
  3. Life expectancy of more than 3 months.
  4. ECOG performance status of 0-2.
  5. Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
  6. ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
  7. 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.
  8. 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.
  9. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
  10. 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.
  11. Voluntary written informed consent.

Exclusion Criteria:

  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, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
  3. Patients who have already started or received post-transplant maintenance or consolidation treatment.
  4. Subject has received daratumumab or other anti-CD38 therapies previously.
  5. Patients not able to tolerate daratumumab or required concomitant medication and procedures.
  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 <50% of predicted normal.
  7. 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).
  8. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  9. Plasma cell leukemia.
  10. Waldenström's macroglobulinemia.
  11. CNS involvement.
  12. Pregnant or lactating females.
  13. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
  14. Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
  15. 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.
  16. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening.
  17. Patient who in investigator's opinion is unable to comply with the protocol requirements.
  18. Uncontrolled hypertension or diabetes.
  19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study.
  20. 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.
  21. 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.
  22. 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.

PREDATOR-MRD:

Inclusion Criteria:

  1. 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 who remain in CR MRD negative. The last response assessment confirming CR MRD negative status based on assessment of bone marrow sample using flow cytometry with sensitivity of at least 10-5 needs to be performed not earlier than 3 months before inclusion to the study.
  2. Males and females ≥18 years of age.
  3. Life expectancy of more than 3 months.
  4. ECOG performance status of 0-2.
  5. Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
  6. ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L.
  7. 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.
  8. 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
  9. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study.
  10. 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.
  11. Voluntary written informed consent.

Exclusion criteria:

  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, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months.
  3. Patients who have already started or received post-transplant maintenance or consolidation treatment.
  4. Subject has received daratumumab or other anti-CD38 therapies previously.
  5. Patients not able to tolerate daratumumab or required concomitant medication and procedures.
  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 <50% of predicted normal.
  7. 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).
  8. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  9. Plasma cell leukemia.
  10. Waldenström's macroglobulinemia.
  11. CNS involvement.
  12. Pregnant or lactating females.
  13. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area.
  14. Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery.
  15. 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.
  16. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12- lead ECG during screening.
  17. Patient who in investigator's opinion is unable to comply with the protocol requirements.
  18. Uncontrolled hypertension or diabetes.
  19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study.
  20. 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.
  21. 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.
  22. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03697655


Contacts
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Contact: Krzysztof Jamroziak, MD, PhD +48 504 065 262 k.m.jamroziak@gmail.com
Contact: Dominik Dytfeld, MD, PhD +48 602 464 708 dytfeld@me.com

Locations
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Poland
Instytut Hematologii i Transfuzjologii Recruiting
Warszawa, Mazowieckie, Poland, 02-776
Contact: Krzysztof Jamroziak, MD, PhD    +48 22 349 64 78    k.m.jamroziak@gmail.com   
Szpital Kliniczny Przemienienia Pańskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu; Oddział Hematologii i Transplantacji Szpiku Recruiting
Poznań, Wielkopolskie, Poland, 60-569
Contact: Dominik Dytfeld, MD, PhD    +48 602464708    dytfeld@me.com   
Sponsors and Collaborators
Polish Myeloma Consortium
Janssen-Cilag Ltd.
Bioscience, S.A.
Investigators
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Principal Investigator: Krzysztof Jamroziak, MD, PhD Polish Myeloma Consortium

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Responsible Party: Polish Myeloma Consortium
ClinicalTrials.gov Identifier: NCT03697655    
Other Study ID Numbers: PMC008
First Posted: October 5, 2018    Key Record Dates
Last Update Posted: January 3, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Neoplastic Processes
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs