Overview

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

Status:
Recruiting
Trial end date:
2024-07-01
Target enrollment:
0
Participant gender:
All
Summary
PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM).
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Polish Myeloma Consortium
Collaborators:
Bioscience, S.A.
Janssen-Cilag Ltd.
Treatments:
Antibodies, Monoclonal
Daratumumab
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.