Evaluation of Motixafortide and G-CSF Versus Placebo and G-CSF for Hematopoietic Stem Cell Mobilization in Multiple Myeloma Patients
- Trial ID
- 2024-511953-23-00
- Protocol
- BL-8040.SCM.301
- Sponsor
- Bioline Rx Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **superiority** of one dose of BL-8040 combined with G-CSF over placebo combined with G-CSF in mobilizing ≥6.0 x 106 CD34+ cells/kg in up to two apheresis sessions. This is in preparation for autologous hematopoietic cell transplantation (auto-HCT) in subjects with multiple myeloma. The clinical relevance of this objective lies in its potential to improve the efficiency and success rate of stem cell mobilization, which is critical for effective transplantation outcomes in multiple myeloma patients.
Secondary objectives include: - Demonstrating the superiority of one dose of BL-8040 + G-CSF over placebo + G-CSF to mobilize ≥2.0 x 106 CD34+ cells/kg in one apheresis session. - Demonstrating the superiority of one dose of BL-8040 + G-CSF over placebo + G-CSF to mobilize ≥6.0 x 106 CD34+ cells/kg in one apheresis session. - Descriptively assessing the comparability between the effects of BL-8040 + G-CSF and placebo + G-CSF in time to neutrophil engraftment, platelet engraftment, and the later of the two. - Descriptively assessing the comparability between the effects of BL-8040 + G-CSF and placebo + G-CSF on graft durability at 60 days, 100 days, and 6, 9, and 12 months post-transplantation. - Demonstrating that the use of BL-8040 + G-CSF results in a reduction in resource use and cost savings compared to placebo + G-CSF.
Participants
The clinical trial involves a total of **78 participants** diagnosed with **Multiple Myeloma**, who are undergoing **Hematopoietic Stem Cell mobilization** for autologous transplantation. The study population includes both male and female subjects, aged between 18 and 78 years. Participants were selected based on specific inclusion criteria, including a histologically confirmed diagnosis of Multiple Myeloma and eligibility for autologous hematopoietic stem cell transplantation. The trial requires participants to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Adequate organ function is a prerequisite, with specific hematology, renal, hepatic, and coagulation parameters defined. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraception guidelines if of childbearing potential. The trial does not specify any particular lifestyle habits or restrictions beyond the medical criteria outlined.
Plans and Procedures
The clinical trial is a **Phase III**, randomized, double-blind, placebo-controlled, multi-center study designed to evaluate the safety, tolerability, and efficacy of a combination treatment involving **Motixafortide** and G-CSF compared to placebo and G-CSF for the mobilization of hematopoietic stem cells in subjects with **multiple myeloma**. The primary objective is to demonstrate the superiority of the combination treatment in mobilizing ≥6.0 x 10^6 CD34+ cells/kg in up to two apheresis sessions in preparation for autologous hematopoietic cell transplantation. The trial is expected to run from April 2018 to September 2028, with participant involvement lasting up to the completion of the transplantation process and follow-up assessments.
Participants will undergo a sequence of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, medical history, and organ function. Following successful screening, participants will be randomized to receive either the investigational treatment or placebo. The study includes multiple follow-up visits to monitor safety and efficacy endpoints, such as the proportion of subjects achieving the target CD34+ cell count and the time to neutrophil and platelet engraftment post-transplantation. The end-of-study visit will assess long-term outcomes, including graft durability at various intervals up to 12 months post-transplantation.
Participant involvement is expected to last from the initial screening through the final follow-up visit, with conditions for early termination including withdrawal of consent, adverse events, or failure to meet continuation criteria. The trial's design ensures rigorous assessment of the investigational treatment's impact on stem cell mobilization and transplantation outcomes, contributing valuable data to the field of hematopoietic stem cell transplantation in multiple myeloma.
Treatment
The clinical trial involves the administration of **MOTIXAFORTIDE**, a solution for injection, as the experimental medication. MOTIXAFORTIDE is a protein-based therapeutic agent, also known by its sponsor product code BL-8040. It is administered subcutaneously at a maximum daily dose of 1.25 mg/kg, with a total maximum dose of 2.5 mg/kg over a treatment period of up to 2 days. The pharmaceutical form is a solution for injection, and the administration is conducted under controlled conditions to ensure participant safety and compliance. The primary objective is to evaluate the efficacy of MOTIXAFORTIDE in combination with G-CSF for the mobilization of hematopoietic stem cells in subjects with multiple myeloma.
The study also includes a **placebo** group, where participants receive a placebo formulation designed to mimic the experimental treatment. The placebo is a sterile, non-pyrogenic lyophilized powder containing 50 mg of mannitol per vial. It is reconstituted with 2 mL of 0.45% Sodium Chloride for Injection (Half Normal Saline) and administered subcutaneously. This placebo is used to maintain the double-blind nature of the trial, ensuring unbiased assessment of the treatment's efficacy and safety. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the proportion of subjects mobilizing ≥6.0 x 106 **CD34+ cells/kg** with up to two apheresis sessions in preparation for autologous hematopoietic cell transplantation (auto-HCT) after administration of G-CSF combined with either a single dose of BL-8040 or placebo. Secondary efficacy endpoints include the proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in one apheresis session and the proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in one apheresis session.
Additional secondary efficacy endpoints will evaluate the time from transplantation to neutrophil engraftment, defined as an absolute neutrophil count (ANC) ≥0.5 x 109/L for three consecutive days or ≥1.0 x 109/L for one day following the conditioning regimen-associated nadir. The time from transplantation to platelet engraftment will also be assessed, defined as the first of three consecutive measurements of platelet count ≥20 x 109/L without platelet transfusion support for seven days following the conditioning regimen-associated nadir. Furthermore, the time from transplantation to engraftment, defined as the time to neutrophils and platelets engraftment, whichever comes later, will be measured. Graft durability will be evaluated at 60 days, 100 days, 6 months, 9 months, and 12 months post-transplantation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients must be between the ages of 18 and 78 years.
- Patients must have a signed study informed consent prior to entering the study.
- Histologically confirmed Multiple Myeloma prior to enrollment and randomization.
- 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.
- Eligible for Autologous Hematopoietic stem cell transplantation according to the Investigator's discretion.
- The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- 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
- 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.
- 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.
- 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.
Exclusion Criteria
- Previous history of autologous or allogeneic-HCT.
- Failed previous HSC collections or collection attempts.
- 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
- Received >6 cycles lifetime exposure to thalidomide or lenalidomide.
- Received >8 cycles of alkylating agent combinations
- Received > 6 cycles of melphalan.
- Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium).
- Received prior treatment with venetoclax
- Plans to receive maintenance treatment within 60 days posttransplantation (e.g. lenalidomide, bortezomib, pomalidomide, thalidomide, carfilzomib, etc.).
- 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.
- Known active CNS metastases or carcinomatous meningitis.
- 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.
- Has an active infection requiring systemic therapy or uncontrolled infection.
- Has a known additional malignancy that is progressing or requires active treatment.
- Has an underlying medical condition that would preclude study participation.
- 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.
- O2 saturation < 92% (on room air).
- Personal history or family history of Long QT Syndrome or Torsade de Pointes
- History of unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden cardiac death.
- 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.
- ECG at screening showing QTcF > 470 msec and/or PR > 280 msec.
- 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.
- 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.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- 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.
- Has a known history of HIV (HIV 1/2 antibodies).
- 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).
- Untreated or unsuccessfully treated Hepatitis B or C.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 20 Apr 2018 | 3 |
 Hungary | Not Recruiting | 20 Apr 2018 | 16 |
 Italy | Not Recruiting | 20 Apr 2018 | 17 |
 Spain | Not Recruiting | 20 Apr 2018 | 8 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
MOTIXAFORTIDE | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 1.25 | 2 | PRD11183566 |
BL-8040 Placebo is formulated as a sterile and non-pyrogenic lyophilized powder in a vial containing 50 mg of mannitol. BL-8040 Placebo should be administrated SC following reconstitution with 2 mL 0.45% Sodium Chloride for Injection (Half Normal Saline). | Placebo | N/A | — | — | — | N/A |