Trial Title:
A Pharmacodynamic Study of the Apheresis Product of Multiple Myeloma Patients Undergoing Quad-induction Followed by Motixafortide + G-CSF Mobilization
NCT ID:
NCT06547112
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Conditions: Keywords:
Hematopoietic stem cell mobilization
CXCR4 inhibition
Motixafortide
Multiple Myeloma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
The study will comprise 2 cohorts enrolled sequentially, each with 10 subjects. The first
10 patients will be enrolled to Cohort 1, and the next 10 patients will be enrolled to
Cohort 2.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Motixafortide
Description:
Dose = 1.25 mg/kg via subcutaneous injection
Arm group label:
Cohort 1: Standard dosing
Arm group label:
Cohort 2: Early dosing
Other name:
BL-8040
Intervention type:
Drug
Intervention name:
G-CSF
Description:
Dose = ~10 µg/kg (and maximum of 15 µg/kg) via subcutaneous injection
Arm group label:
Cohort 1: Standard dosing
Arm group label:
Cohort 2: Early dosing
Summary:
This study includes extended CD34+ profiling on the apheresis product of multiple myeloma
patients undergoing standard-of-care quad-induction followed by motixafortide + G-CSF
mobilization, and in addition, assesses the pharmacodynamics (PD) of motixafortide
following "standard" (~12 hours) vs "early" (~16 hours) dosing. The investigators
hypothesize that quad-induction may alter the stem cell subsets within the mobilized
graft. The investigators further hypothesize that standard and early dosing strategies
will result in comparable mobilization and stem cell collection rates.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects must be between the ages of 18 and 78 years, inclusive.
- Histologically confirmed multiple myeloma expected to receive high-dose chemotherapy
(HDT) and autologous stem cell transplantation (ASCT)
- Received ≥3 cycles but ≤6 cycles of daratumumab-based quadruplet induction therapy
(quadruplet induction therapy: combining daratumumab, a proteasome inhibitor, an
IMiD, and dexamethasone) before ASCT
- At least one week (7 days) from last induction cycle prior to the first dose of
G-CSF for mobilization
- The subjects should be in first or second CR (including CR and SCR) or PR (including
PR and VGPR)
- ECOG performance status 0 or 1
- Adequate organ function at screening as defined below:
- White blood cell (WBC) counts > 2.5 × 10^9/L
- Absolute neutrophil count > 1.5 K/cumm
- Platelet count >100 K/cumm
- GFR value of ≥15 mL/min/1.732 (by MDRD equation)
- ALT and/or AST ≤2.5 × ULN
- Total bilirubin ≤2.0 × ULN unless the participant has Gilbert disease
- INR or PT: ≤1.5 × ULN unless participant is receiving anticoagulant therapy, as
long as PT or PTT is within therapeutic range of intended use of anticoagulants
- aPTT: ≤1.5 × ULN unless participant 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
or serum pregnancy test within 7 days prior to G-CSF first administration.
Non-childbearing potential is defined as (by other than medical reasons):
- ≥45 years of age and has not had menses for over 2 years
- Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral
tubal ligation at least 6 weeks prior to screening
- 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
- Vasectomized partner
- Sexual abstinence These methods must be used starting at study enrollment and for
the duration of study participation through 8 days after the last dose of
motixafortide.
Male subjects must agree to use an adequate method of contraception (barrier method)
starting with the first day of G-CSF administration through 8 days after the last dose of
motixafortide.
- Ability to understand and willingness to sign an IRB approved written informed
consent document.
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:
- Dexamethasone: 7 days
- Thalidomide: 7 days
- Lenalidomide: 7 days
- Pomalidomide: 7 days
- Bortezomib: 7 days
- Carfilzomib: 7 days
- Ixazomib: 7 days
- G-CSF: 14 days
- GM-CSF or pegfilgrastim: 21 days
- Erythropoietin or erythrocyte-stimulating agents: 30 days
- Eltrombopag, romiplostim or platelet-stimulating agents: 30 days
- Carmustine (BCNU): 42 days/6 weeks
- Received >6 cycles lifetime exposure to an IMiD
- 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
- 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 motixafortide, G-CSF or other agents used in the study
- Has an active or uncontrolled infection requiring systemic therapy
- Has a known additional malignancy that is progressing or requires active treatment
- Has a known underlying medical condition that, in the opinion of the treating
physician or Principal Investigator, would preclude study participation.
- Is currently participating in an investigational treatment study, or has
participated in a study of an investigational agent and received study therapy, or
has been treated with an investigational device, within 4 weeks prior to 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.
- History of myocardial infarction, CABG, coronary or cerebral artery stenting and/or
angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart
failure within 3 months prior to study enrollment, 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 participant has an implanted pacemaker or implantable cardiac
defibrillator (ICD) with backup pacing capabilities.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial, in the opinion of the treating
physician or Principal Investigator.
- 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 8 days after the last dose of study drug.
- HIV-infected if not on effective anti-retroviral therapy with undetectable viral
load for 6 months. Patients with HIV who are receiving effective anti-retroviral
therapy and have had an undetectable viral load for at least 6 months are eligible.
- Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive
therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral
load on suppressive therapy are eligible.
- History of hepatitis C virus (HCV) infection that has not been cured or that has a
detectable viral load. Patients with a history of HCV that has been treated and
cured are eligible. Patients with HCV infection who are currently on treatment and
have an undetectable HCV viral load are eligible.
Gender:
All
Minimum age:
18 Years
Maximum age:
78 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Zachary Crees, M.D.
Phone:
314-747-8076
Email:
zcrees@wustl.edu
Investigator:
Last name:
Zachary Crees, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Matthew Christopher, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
John F DiPersio, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Mark Schroeder, M.D., MSCI
Email:
Sub-Investigator
Investigator:
Last name:
Keith Stockerl-Goldstein, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Ravi Vij, M.D.
Email:
Sub-Investigator
Start date:
October 31, 2024
Completion date:
January 31, 2026
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
BioLineRx, Ltd.
Agency class:
Industry
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06547112
http://www.siteman.wustl.edu
