MOTIXAFORTIDE for Multiple myeloma

Stratification factors

• Remission status (Complete remission (CR) vs. Partial Remission (PR))
• Baseline platelet count (<200 x 10^9/L vs ≥200 x 10^9/L)

Inclusion criteria

• {"criterion_text":"- Patients must be between the ages of 18 and 78 years.\n- Women of childbearing potential must agree to use 2 methods of effective contraception: One barrier method (e.g. diaphragm, or condom or sponge, each of which are to be combined with a spermicide) and one hormonal method, unless she uses a highly effective method. Highly effective methods of contraception include: • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable • Intrauterine device (IUD) • Intrauterine hormone-releasing system (IUS) • Bilateral tubal occlusion • Vasectomised partner • Sexual abstinence These methods must be used prior to study entry and for the duration of study participation through 30 days after the last dose of study treatment. Non-childbearing potential is defined as (by other than medical reasons): • ≥45 years of age and has not had menses for over 2 years. • Amenorrheic for > 2 years without a hysterectomy and oophorectomy and a Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pre-trial (screening) evaluation. • Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation at least 6 weeks prior to screening. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure; otherwise the subject must be willing to use two adequate barrier methods throughout the study, starting with the Screening Visit, through 30 days after the last dose of study drug. Information must be captured appropriately within the site's source documents.\n- Male subjects must agree to use an adequate method of contraception starting with the first day of G-CSF administration through 30 days after the last dose of study drug.\n- Patients must have a signed study informed consent prior to entering the study.\n- Histologically confirmed Multiple Myeloma prior to enrollment and randomization.\n- At least one week (7 days) from last induction cycle of combination/multi-agent chemotherapy (e.g. KRD [carfilzomib, lenalidomide, dexamethasone] or VRD [bortezomib, lenalidomide, dexamethasone]) or from last single agent chemotherapy (e.g. lenalidomide, pomalidomide, bortezomib, dexamethasone, etc) prior to the first dose of G-CSF for mobilization.\n- Eligible for Autologous Hematopoietic stem cell transplantation according to the Investigator's discretion.\n- The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR).\n- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n- Adequate organ function at screening as defined below: a. Hematology: • White blood cell counts more than 2.5 x 10^9/L • Absolute neutrophil count more than 1.5 x 10^9/L • Platelet count more than 100 x10^9/L b. Renal Function: • GFR value of ≥15 mL/min/1.73^2 calculated by MDRD equation c. Hepatic function: • ALT and/or AST ≤ 2.5 x ULN • Total Bilirubin ≤ 2.0 x ULN unless the subject has Gilbert disease d. Coagulation test: • INR or PT: ≤1.5xULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants • aPTT: ≤1.5xULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants\n- Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative serum pregnancy test at screening and negative urine/serum pregnancy test within 72 hours prior to G-CSF first administration."}

Exclusion criteria

• {"criterion_text":"- Previous history of autologous or allogeneic-HCT.\n- Has received a live vaccine within 30 days of the planned start of G-CSF administration. Seasonal flu vaccines that do not contain live virus are permitted.\n- Known active CNS metastases or carcinomatous meningitis.\n- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BL-8040, G-CSF, or other agents used in the study.\n- Has an active infection requiring systemic therapy or uncontrolled infection.\n- Has a known additional malignancy that is progressing or requires active treatment.\n- Has an underlying medical condition that would preclude study participation.\n- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.\n- O2 saturation < 92% (on room air).\n- Personal history or family history of Long QT Syndrome or Torsade de Pointes\n- History of unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden cardiac death.\n- Failed previous HSC collections or collection attempts.\n- Myocardial infarction, CABG, coronary or cerebral artery stenting and/or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Angina Pectoris Class >2 or NYHA Heart Failure Class >2.\n- ECG at screening showing QTcF > 470 msec and/or PR > 280 msec.\n- Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block, unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.\n- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.\n- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n- Is pregnant or breast feeding or expecting to conceive or women of childbearing potential unless consent to use two contraceptive methods or highly effective contraception as detailed above, within the projected duration of the trial, starting with the Screening Visit through 30 days after the last dose of study drug.\n- Has a known history of HIV (HIV 1/2 antibodies).\n- Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] reactive) or Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is detected).\n- Untreated or unsuccessfully treated Hepatitis B or C.\n- Taken any of the listed below concomitant medications, growth factors or stimulating agents within the designated washout period: a. Dexamethasone: 7 days b. Thalidomide: 7 days c. Lenalidomide: 7 days d. Pamolidomide: 7 days e. Bortezomib: 7 days f. Carfilzomib: 7 days g. G-CSF: 14 days h. GM-CSF or Neulasta®: 21 days i. Erythropoietin or erythrocyte stimulating agents: 30 days j. Eltrombopag, romiplostim or platelet stimulating agents: 30 days k. Carmustine (BCNU): 42 days/6 weeks l. Daratumumab: 28 days m. Ixazomib: 7 days\n- Received >6 cycles lifetime exposure to thalidomide or lenalidomide.\n- Received >8 cycles of alkylating agent combinations\n- Received > 6 cycles of melphalan.\n- Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium).\n- Received prior treatment with venetoclax\n- Plans to receive maintenance treatment within 60 days posttransplantation (e.g. lenalidomide, bortezomib, pomalidomide, thalidomide, carfilzomib, etc)."}

Primary endpoints

• {"endpoint_text":"- Efficacy Endpoint: Proportion of subjects mobilizing ≥6.0 x 10^6 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after G-CSF + single administration of BL-8040 or placebo.","definition_or_measurement_approach":"Proportion of subjects achieving a collection of ≥6.0 x 10^6 CD34+ cells/kg measured from up to two apheresis sessions following mobilization with G-CSF plus single administration of BL-8040 or placebo."}

Secondary endpoints

• {"endpoint_text":"- Efficacy Endpoint: Proportion of subjects who collect ≥2.0 x 10^6 CD34+ cells/kg in 1 apheresis session.","definition_or_measurement_approach":"Proportion of subjects collecting ≥2.0 x 10^6 CD34+ cells/kg in a single apheresis session."}
• {"endpoint_text":"- Efficacy Endpoint: Proportion of subjects who collect ≥6.0 x 10^6 CD34+ cells/kg in 1 apheresis session.","definition_or_measurement_approach":"Proportion of subjects collecting ≥6.0 x 10^6 CD34+ cells/kg in a single apheresis session."}
• {"endpoint_text":"- Additional Secondary Efficacy Endpoints: Time from transplantation to neutrophil engraftment, defined as ANC ≥ 0.5 x 10^9/L for 3 consecutive days or ≥1.0 x 10^9/L for 1 day following the conditioning regimen associated nadir.","definition_or_measurement_approach":"Time (days) from transplantation to neutrophil engraftment defined as ANC ≥0.5 x 10^9/L for 3 consecutive days or ≥1.0 x 10^9/L for 1 day following the conditioning-regimen nadir."}
• {"endpoint_text":"- Time from transplantation to platelet engraftment, defined as the first of 3 consecutive measurements of platelet count ≥20 x 10^9/L without platelet transfusion support for 7 days following the conditioning regimen associated nadir.","definition_or_measurement_approach":"Time (days) from transplantation to platelet engraftment defined as first of 3 consecutive platelet counts ≥20 x 10^9/L without platelet transfusion support for 7 days after conditioning-regimen nadir."}
• {"endpoint_text":"- Time from transplantation to engraftment, defined as the time to neutrophils and platelets engraftment, whichever comes later.","definition_or_measurement_approach":"Time (days) from transplantation to the later of neutrophil or platelet engraftment as defined in the protocol."}
• {"endpoint_text":"- Graft durability at 60 days post-transplantation.","definition_or_measurement_approach":"Assessment of graft durability at 60 days after transplantation (protocol-defined measure of sustained engraftment/status)."}
• {"endpoint_text":"- Graft durability at 100 days post-transplantation.","definition_or_measurement_approach":"Assessment of graft durability at 100 days after transplantation."}
• {"endpoint_text":"- Graft durability at 6 months post-transplantation.","definition_or_measurement_approach":"Assessment of graft durability at 6 months after transplantation."}
• {"endpoint_text":"- Graft durability at 9 months post-transplantation.","definition_or_measurement_approach":"Assessment of graft durability at 9 months after transplantation."}
• {"endpoint_text":"- Graft durability at 12 months post-transplantation.","definition_or_measurement_approach":"Assessment of graft durability at 12 months after transplantation."}

Spain

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

18-07-2024

Processing Time Days

13

Number Of Sites

3

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

13-02-2025

Processing Time Days

223

Number Of Sites

2

Number Of Participants

17

Germany

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

10-01-2025

Processing Time Days

189

Number Of Sites

1

Number Of Participants

3

Hungary

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

648

Number Of Sites

2

Number Of Participants

16

Primary sponsor

Full Name

Bioline Rx Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Israel

Contract research organisations

Name

FGK Clinical Research Kft.

Name

FGK Clinical Research GmbH

Name

IQVIA RDS Spain S.L.

Name

Iqvia Rds Italy S.r.l.

Name

Medidata Solutions Inc.

Third parties

• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"Central Lab: Myeloma cells in apheresis product","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eurofins Pharma Bioanalytics Services US Inc.","duties_or_roles":"Central Lab: ADA for BL-8040","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"Central Lab: Complement","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clario","duties_or_roles":"Central ECG","organisation_type":"Health care"}
• {"country":"Italy","full_name":"Iqvia Rds Italy S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Bioforum Ltd.","duties_or_roles":"Biometrics","organisation_type":"Health care"}
• {"country":"Spain","full_name":"IQVIA RDS Spain S.L.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eurofins Lancaster Laboratories Inc.","duties_or_roles":"Central Lab: Tryptase","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Hungary","full_name":"FGK Clinical Research Kft.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EVERSANA Life Science Services LLC","duties_or_roles":"","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Allucent (DE) GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q2 Solutions Ltd.","duties_or_roles":"Central Lab for primary endpoint: Flow Cytometry","organisation_type":"Health care"}
• {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"Central Lab: PK analysis of BL-8040 (part 1 and part 2)","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"StatExcellence","duties_or_roles":"","organisation_type":"Health care"}