Relapsed/Refractory Multiple Myeloma Clinical Trial
— SMR-3184Official title:
Phase I, Open Label, Dose Escalation Study to Investigate the Tolerability and Efficacy of APO010 in Patients With Relapsed/Refractory Multiple Myeloma Selected by Drug Response Predictor (DRP)
Verified date | January 2020 |
Source | Oncology Venture |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Multicentre, open label, uncontrolled, phase I pharmacokinetic study, to determine the Maximum Tolerated Dose (MTD) of APO010 administered intravenously on D1, D8 and D15 followed by a one-week drug rest, in patients with multiple myeloma for who have relapsed or are refractory to 2 (in high-risk patients 1) or more different prior therapies and who have Drug Response Predictor (DRP) for APO010 indicating a higher likelihood for response to APO010. The study will contain an extension phase where the recommended Dose will be tested on additional patients.
Status | Terminated |
Enrollment | 1 |
Est. completion date | January 16, 2020 |
Est. primary completion date | January 16, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Relapsed or relapsed/refractory to 2 (in high-risk patients 1) or more different prior therapies, including IMiDs and PI - Measurable disease - Serum M-protein > 10 g/l, or - Urine M-protein > 200 mg/24 hours, or - Serum involved-FLC (iFLC) > 100 mg/l and abnormal FLC ratio - Have participated in the APO010 screening protocol in which Drug Response Predictor (DRP) outcome is measured as being in the upper likelihood of response (50% in dose-finding part and 25% in the expansion cohort) - Age > 18 years - Adequate organ and bone marrow function as defined below: - Absolute neutrophil count > 1.5 x 109/l (> 0.75 x 109/l in case > 50% plasma cell count in bone marrow) - Platelet count > 50 x 109/l (> 30 x 109/l in case > 50% plasma cell count in bone marrow) - Haemoglobin > 4.6 mmol/l (> 7.5 g/l) - Bilirubin = upper limit of normal - aspartate aminotransferase (SGOT)/alanine transaminase (SGPT) = upper limit of normal - Creatinine < 1.5 x upper limit of normal or creatinine clearance > 50 ml/min calculated according to Cockcroft-Gault - Eastern Cooperative Oncology Group (ECOG) performance status < 2 - Life expectancy of at least 3 months. - Capability of understanding the nature of the study and giving written informed consent - Signed informed consent form Exclusion Criteria: - Have central nervous system (CNS) myeloma - Have plasma cell leukaemia defined as plasma cell count > 2000 / µL in peripheral blood - Have symptomatic amyloidosis - Have anti-myeloma treatment or radiotherapy within 3 weeks from first infusion - Have received a cumulative dose of corticosteroid > 200 mg (dexamethasone, or equivalent dose of prednisone) within 2 weeks of the first infusion - Have received any experimental drug or experimental therapy within 3 weeks before the first infusion - Have received autologous-stem cell transplantation (SCT) within 12 weeks before the first infusion - Have received an allogeneic stem cell transplantation (SCT) - Have had past or current malignancy except for: - Cervical carcinoma < Stage 1B - Non-invasive basal cell or squamous cell skin carcinoma - Malignant melanoma with CR of > 10 years - Any other curable cancer with a CR > 5 years - Have major surgery within 4 weeks prior to the first infusion - Have severe infection requiring iv treatment - Have known HIV positivity - Have known active hepatitis B or C - Have had clinical significant arteriosclerotic events: - Ischemic heart disease - Unstable angina - Myocardial infarction - Transient ischemic attack - Ischemic stroke - Documented peripheral arteriosclerosis - Have baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec for female patients or > 450 msec for male patients or a complete left bundle branch block (defined as QRS interval > 120 msec in left bundle branch block form) - CNS disease including epilepsy or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures - Women of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Male patients or male patients who have female partners of childbearing age and potential who are not willing to use effective contraception during the study and at least until 90 days after last dose of study drug. Highly effective methods of birth control are defined as those which result in a low failure rate, i.e., less than 1% per year, when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomized partner - Pregnant or breast-feeding women |
Country | Name | City | State |
---|---|---|---|
Denmark | University Hospital of Copenhagen | Copenhagen |
Lead Sponsor | Collaborator |
---|---|
Oncology Venture | Medical Prognosis Institute A/S, Smerud Medical Research International AS |
Denmark,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Tolerated Dosage | To define the Maximum Tolerated Dosage of intravenous bolus administration of APO010 | 1 Year | |
Primary | Recommended Dosage | To define the Recommended Dosage of intravenous bolus administration of APO010 | 1 Year | |
Secondary | Percentage (%) of patients with drug-related adverse events (adverse reactions) | To define the safety profile of a weekly schedule of APO010, including Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.03, Physical examination, vital signs, concomitant medications and laboratory data. To define the safety profile of APO010 after chronic administration (beyond 3 consecutive administrations, i.e., two or more cycles) and to define local toxicity at the site of administration through observation of the area of infusion. | 1 Year | |
Secondary | The pharmacokinetic profile (AUC INF) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC INF). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The pharmacokinetic profile (AUC last) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC last). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The pharmacokinetic profile (AUC 0-12hr) for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated are Area Under the curve (AUC 0-12hr). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The Maximum Plasma Concentration (Cmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is Maximum Plasma Concentration (Cmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The Observed maximum (Tmax), for APO010 at doses above 60 µg/m2 | The PK variable that will be evaluated is, time of observed maximum (Tmax). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The Terminal half-life (T½), for APO010 at doses above 60 µg/m2 | Pharmacokinetic (PK) parameters will be calculated or estimated by using a model independent approach. The PK variable that will be evaluated is the terminal half-life (T½)). Pharmacokinetic parameters will be measured for APO010 at doses above 60 µg/m2 | 1 Year | |
Secondary | The HADA Antibody Response | Assays will be performed to detect the production of antibodies against APO010 (HADA) in the serum of treated patients. If antibodies are formed, their ability to neutralize the biological activity of APO010 in in vitro cytotoxicity assay will be measured. | 1 Year | |
Secondary | The Tumor Response | Using International Myeloma Working Group (IMWG) response criteria, based on measurements in blood and urine and in case of disappearance of M-proteins with additional confirmatory bone-marrow investigation, the number of patients with either stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) or progressive disease (PD) will be measured. | 1 Year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05427812 -
Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT04093596 -
Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)
|
Phase 1 | |
Not yet recruiting |
NCT05498545 -
Universal BCMA-targeted LUCAR-B68 Cells in Patients With Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT04973605 -
A Phase 1b/2 Study of BGB-11417in Monotherapy and in Various Combinations With Dexamethasone and Carfilzomib in Multiple Myeloma
|
Phase 1/Phase 2 | |
Recruiting |
NCT05376345 -
BCMA-targeted LCAR-BCDR Cells in Patients With Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Withdrawn |
NCT05980507 -
An Open Label, Single-arm Clinical Study Evaluating the Safety and Efficacy of ICI201 Infusion in Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Active, not recruiting |
NCT04601935 -
A Single-center Exploratory Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of a BCMA-targeted Universal LCAR-BCX Cells in Patients With Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Terminated |
NCT06160609 -
Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM
|
Phase 1/Phase 2 | |
Completed |
NCT03309111 -
Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT06049290 -
A Phase I/II Clinical Trial of LBL-034 in Patients With Relapsed Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
Recruiting |
NCT05259839 -
A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Terminated |
NCT03318861 -
Study to Evaluate the Safety and Efficacy of KITE-585 in Participants With Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Active, not recruiting |
NCT03590652 -
Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as Salvage Therapy in Relapsed/Refractory Multiple Myeloma
|
Phase 2 | |
Completed |
NCT01794520 -
Study Evaluating ABT-199 in Participants With Relapsed or Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
Terminated |
NCT04142619 -
Study Evaluating Safety and Efficacy of UCART Targeting CS1 in Patients With Relapsed/Refractory Multiple Myeloma (MELANI-01)
|
Phase 1 | |
Completed |
NCT01849848 -
Study of SyB L-0501 to Treat Relapsed/Refractory Multiple Myeloma
|
Phase 2 | |
Completed |
NCT01794507 -
A Study Evaluating ABT-199 in Multiple Myeloma Subjects Who Are Receiving Bortezomib and Dexamethasone as Standard Therapy
|
Phase 1 | |
Recruiting |
NCT05160584 -
A Study of Real-Life Current Standards of Care in Participants With Relapsed and/or Refractory Multiple Myeloma
|
||
Terminated |
NCT03287908 -
A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT05862012 -
Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma
|
Phase 1 |