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A Phase III, Safety, Tolerability and Efficacy of Combination Treatment of BL-8040 and G-GSF as Compared to Placebo and G-CSF for thE MobilizatioN of HematopoiEtic Stem Cells for Autologous TransplantatIon in SubjectS With MM (GENESIS)

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ClinicalTrials.gov Identifier: NCT03246529
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):
BioLineRx, Ltd.

Brief Summary:
A total of 207 subjects will be randomized into the study which will employ a double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: BL-8040 1.25mg/kg + G-CSF Drug: Placebo +G-CSF Phase 3

Detailed Description:
  • Part 1: This lead-in period designed to ascertain the dose of BL-8040 will enroll a total of up to 30 subjects to an open labeled treatment to assess the efficacy, safety, PK and PD parameters of treatment with G-CSF 10 µg/kg/day and BL-8040 1.25mg/kg, per study protocol to goal collection of ≥ 6x106 CD34+ cells/kg.
  • Part 2: Following the successful completion of Part 1, a total of 177 subjects will be randomized into Part 2 of the study which will employ a double-blind placebo-controlled setting to assess the efficacy and safety of G-CSF + BL-8040 as compared to G-CSF + placebo.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: subjects will be randomized using a 2:1 ratio to receive G-CSF + BL-8040 or G-CSF + Placebo, respectively. Randomization will use permuted blocks stratifying subjects by US geographical region (NorthEast, SouthEast, MidWest, SouthWest and NorthWest), remission status (CR vs. PR), and baseline platelet count (< 200 X 109/L or ≥ 200 X 109/L).
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Placebo-Controlled, Multi-Centre Study Evaluating the Safety, Tolerability and Efficacy of Combination Treatment of BL-8040 and G-GSF as Compared to Placebo and G-CSF for thE MobilizatioN of HematopoiEtic Stem Cells for Autologous TransplantatIon in SubjectS With Multiple Myeloma - The GENESIS Study
Estimated Study Start Date : January 18, 2018
Estimated Primary Completion Date : April 22, 2019
Estimated Study Completion Date : September 22, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: BL-8040 1.25mg/kg + G-CSF
double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.
Drug: BL-8040 1.25mg/kg + G-CSF
Up to 2 SC injections of BL-8040 are anticipated during the study. Injections of G-CSF per standard of care

Active Comparator: Placebo + G-CSF
double-blind placebo-controlled setting designed to assess the safety, tolerability and efficacy of G-CSF + BL-8040 as compared to G-CSF + Placebo, for stem cell mobilization in MM.
Drug: Placebo +G-CSF
Up to 2 SC injections of Placebo are anticipated during the study. Injections of G-CSF per standard of care




Primary Outcome Measures :
  1. Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions [ Time Frame: 18 months ]
    Proportion of subjects mobilizing ≥6.0 x 106 CD34+ cells/kg with up to 2 apheresis sessions in preparation for auto-HCT after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.


Secondary Outcome Measures :
  1. Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session [ Time Frame: 18 months ]
    Proportion of subjects who collect ≥2.0 x 106 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.

  2. Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session [ Time Frame: 18 months ]
    Proportion of subjects who collect ≥6.0 x 106 CD34+ cells/kg in 1 apheresis session after treatment with G-CSF + single administration of BL-8040 or G-CSF + placebo.

  3. Time to neutrophil engraftment, after autologous hematopoietic cell transplantation [ Time Frame: 18 months ]
    Time to neutrophil engraftment, after autologous hematopoietic cell transplantation, as defined as ANC ≥0.5 x 109/L for 3 days or ≥1.0 x 109/L for 1 day following the conditioning regimen associated nadir.

  4. Time to platelet engraftment, after autologous hematopoietic cell transplantation [ Time Frame: 18 months ]
    Time to platelet engraftment, after autologous hematopoietic cell transplantation, as defined as the first of 3 consecutive measurements of platelet count ≥20 x 109/L without platelet transfusion support for 7 days following the conditioning regimen associated nadir.

  5. Graft durability at 100 days post engraftment. [ Time Frame: 18 months ]
    Graft durability at 100 days post engraftment, after autologous hematopoietic cell transplantation.



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Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed Multiple Myeloma prior to enrolment and randomization.
  2. At least 4 weeks (112 days) from last induction cycle of combination/multi-agent cyto-reductive chemotherapy and no single agent chemotherapy/maintenance within 7 days (e.g. lenalidomide, pomalidomide, bortezomib, dexamethasone, etc).
  3. Eligible for Autologous Hematopoietic stem cell transplantation according at the investigator discretion.
  4. The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR)
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  6. Adequate organ function at baseline .
  7. Subjects must use effective contraception.

Exclusion Criteria:

  1. Previous history of autologous or allogeneic-HCT
  2. Failed previous HSC collections or collection attempts.
  3. Patients whose apheresis product were to be further selected and purified
  4. Taken any of the listed below concomitant medications, growth factors or stimulating agents within the designated washout period:

    1. Dexamethasone: 7 days
    2. Thalidomide: 7 days
    3. Lenalidomide: 7 days
    4. Pamolidomide: 7 days
    5. Bortezomib: 7 days
    6. Carfilzomib: 7 days
    7. G-CSF: 14 days
    8. GM-CSF or Neulasta®: 21 days
    9. Combination/multi-agent cyto-reductive therapy
    10. Erythropoietin or erythrocyte stimulating agents: 30 days
    11. Eltrombopag, romiplostim or platelet stimulating agents: 30 days
    12. Carmustine (BCNU): 42 days/6 weeks
  5. Received >6 cycles lifetime exposure to Lenalidomide.
  6. Received >2 cycles of alkylating agent combinations.
  7. Received 3-bis(2-chloroethyl)-1nitrosourea (BCNU or Carmustine) within 6 weeks prior to anticipated first dose of G-CSF.
  8. Received prior treatment with radioimmunotherapy, (e.g. radionuclides, holmium).
  9. Received marrow stimulating factors:

    1. Received G-CSF within 14 days prior to anticipated first dose of G-CSF.
    2. Received Pegfilgrastim (GM-CSF or Nulesta) within 3 weeks prior to anticipated first dose of G-CSF.
    3. Received erythrocyte of platelet stimulating agents within 30 days prior to anticipated first dose of G-CSF
  10. Plans to receive maintenance treatment within 100 days post-engraftment (e.g. Lenalidomide, Bortezomib, Pomalidomide, Thalidomide, Carfilzomib, etc.)
  11. Has received a live vaccine within 30 days of the planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.
  12. Known active CNS metastases or carcinomatous meningitis.
  13. 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.

16. 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.

17. 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.

18. O2 saturation < 92% (on room air). 19. History of unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death.

20. History or family history of Long QT Syndrome or Torsade de Pointes. 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 Class 2 Angina Pectoris or NYHA Heart Failure Class >2. QTcF > 470 msec, 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.

21. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

22. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 30 days after the last dose of trial treatment.

23. Has a known history of HIV (HIV 1/2 antibodies), active / chronic Hepatitis B or C.


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): NCT03246529


Contacts
Contact: Inbal Goldstein, Ph.D +972-8-642-9100 ext 374 inbalg@biolinerx.com
Contact: Hemda Chen, PharMD +972-8-642-9100 ext 120 hemdac@biolinerx.com

Locations
United States, Missouri
The Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ryan Monahan, BSC    314-454-8377    rmonahan@wustl.edu   
Sponsors and Collaborators
BioLineRx, Ltd.
Investigators
Principal Investigator: John DiPersio, MD Washington University School of Medicine

Responsible Party: BioLineRx, Ltd.
ClinicalTrials.gov Identifier: NCT03246529     History of Changes
Other Study ID Numbers: BL-8040.SCM.301
First Posted: August 11, 2017    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
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
Lenograstim
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs