Trial Title:
Ph2, Study to Assess the Safety and Efficacy of GPC 100 and Propranolol With and Without G-CSF for the Mobilization of Stem Cells in Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant
NCT ID:
NCT05561751
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Propranolol
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Intervention model description:
This is a randomized, open-label study. Patients will be screened within 28 days prior to
the study drug administration. Patients will be randomly assigned to 1 of 2 treatment
arms prior to study drug administration.
Approximately 40 patients will be randomized in a 1:1 ratio to the following treatment
arms:
- GPC-100 in combination with propranolol; or
- GPC-100 in combination with propranolol and G-CSF.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
GPC-100
Description:
GPC-100 is to be administered at a dose of 3.14 mg/kg GPC-100 free base via IV infusion.
The corresponding volume of the reconstituted GPC-100 solution calculated based on the
patient weight will be administered via IV infusion over 15 min
Arm group label:
GPC-100 in combination with propranolol and G-CSF
Arm group label:
GPC-100 in combination with propranolol;
Intervention type:
Drug
Intervention name:
Propranolol
Description:
propranolol
Arm group label:
GPC-100 in combination with propranolol and G-CSF
Arm group label:
GPC-100 in combination with propranolol;
Intervention type:
Drug
Intervention name:
G-CSF
Description:
G-CSF
Arm group label:
GPC-100 in combination with propranolol and G-CSF
Summary:
This is a randomized, open-label study. Patients will be screened within 28 days prior to
the study drug administration. Patients will be randomly assigned to 1 of 2 treatment
arms prior to study drug administration.
Approximately 40 patients will be randomized in a 1:1 ratio to the following treatment
arms:
- GPC-100 in combination with propranolol; or
- GPC-100 in combination with propranolol and G-CSF. To characterize the safety and
clinical activity of GPC-100, the study will employ a Bayesian Optimal Phase II
(BOP2) design to enroll patients for each arm.
All patients will receive via IV 3.14 mg/kg GPC-100 (Burixafor) at least 2 hours prior to
leukapheresis sessions from Days 7-8 (Days 9-11 optional) and 30 mg propranolol (3 x 10
mg tablets) twice daily at 8:30 AM (+/- 1 hr) and 4:00 PM (+/- 1 hr) local time from Days
1 to 8 (and on Days 9-11, if applicable). Patients will administer the first dose of
propranolol onsite on Day 1. Patients will be provided with doses of propranolol for
self-administration at time points when they are not otherwise required to be onsite.
Sites should contact patients via telephone to confirm propranolol administration for
doses administered outside of clinic.
Detailed description:
This is a randomized, open-label study. Patients will be screened within 28 days prior to
the study drug administration. Patients will be randomly assigned to 1 of 2 treatment
arms prior to study drug administration.
Approximately 40 patients will be randomized in a 1:1 ratio to the following treatment
arms:
- GPC-100 in combination with propranolol; or
- GPC-100 in combination with propranolol and G-CSF. To characterize the safety and
clinical activity of GPC-100, the study will employ a Bayesian Optimal Phase II
(BOP2) design to enroll patients for each arm.
All patients via IV 3.14 mg/kg GPC-100 (Burixafor) at least 2 hours prior to
leukapheresis sessions from Days 7-8 (Days 9-11 optional) and 30 mg propranolol (3 x 10
mg tablets) twice daily at 8:30 AM (+/- 1 hr) and 4:00 PM (+/- 1 hr) local time from Days
1 to 8 (and on Days 9-11, if applicable). Patients will administer the first dose of
propranolol onsite on Day 1. Patients will be provided with doses of propranolol for
self-administration at time points when they are not otherwise required to be onsite.
Sites should contact patients via telephone to confirm propranolol administration for
doses administered outside of clinic.
Only patients randomized to the treatment arm receiving GPC-100 in combination with
propranolol and G-CSF will receive SC injections of 10 microgram/kg/day G-CSF at 5:00 PM
(+/- 3 hr) local time on Days 3 to 7. Patients in this arm will receive G-CSF injections
on Days 8-10 at 5:00 PM (+/- 3 hr) local time only if they will undergo the optional
third-fifth days of mobilization/collection (Days 9-11) at the Investigator's discretion.
On Days 7 and 8 (and on Days 9-11, if applicable), the patient will receive a morning 30
mg propranolol dose (3 x 10 mg tablets) followed immediately by a 3.14 mg/kg dose of
GPC-100 free base (active ingredient) and will start collection of CD34+ stem cells via
leukapheresis.
Criteria for eligibility:
Criteria:
Inclusion Criteria
To be eligible to participate in this study, patients must meet all the following
criteria:
1. Male or female, greater than or equal to18 years of age;
2. Patients with diagnosis of MM per the International Myeloma Working Group criteria ;
3. Eligible for ASCT at the Investigator's discretion;
4. >4 weeks since completion of last cycle of chemotherapy prior to Day 1;
5. Patient must be on first or second complete response or partial response;
6. Eastern Cooperative Oncology Group performance status of 0 or 1 (see Appendix C);
7. Systolic blood pressure (SBP) 100 - 160 mmHg inclusive, and diastolic blood pressure
(DBP) 60 - 100 mmHg inclusive;
8. ANC greater than or equal to1.0 x 109/L on Screening laboratory assessments;
9. Platelet count greater than or equal to100 x 109/L on Screening laboratory
assessments;
10. Creatinine clearance greater than or equal to 30 ml/min, as calculated according to
the Cockcroft-Gault formula;
11. Aspartate aminotransferase and alanine aminotransferase less than or equal to 2 x
upper limit of normal (ULN) and total bilirubin less than or equal to1.5 x ULN on
Screening laboratory assessments;
12. Adequate cardiac (left ventricular ejection fraction [LVEF] greater than or equal to
50%) and pulmonary function (room air O2 saturation value greater than or equal to
92%);
13. For females, 1 of the following criteria must be fulfilled:
1. At least 1 year postmenopausal; or
2. Surgically sterile, or willing to use a double-barrier method of contraception
(e.g., intrauterine device plus condom, spermicidal gel plus condom) from Day 1
until 28 days after the last dose of GPC-100.
14. Males must be willing to use a reliable form of contraception (e.g., use of a condom
or a partner fulfilling the above criteria) from Day 1 until 28 days after the last
dose of GPC-100; and
15. Patients must be willing and able to provide signed informed consent. 4.2 Exclusion
Criteria
Patients must be excluded if they meet any of the following criteria:
1. greater than or equal to 25% of BM irradiated within 5 years prior to Day 1 (see
Appendix D);
2. No more than one year of therapy administered prior to stem cell mobilization, per
institution standards;
3. Patients who have undergone previous stem cell transplant;
4. Receipt of G-CSF within 2 weeks prior to Day 1;
5. History of another malignancy except for the following:
1. Adequately treated local basal cell or squamous cell carcinoma of the skin;
2. Adequately treated carcinoma in situ of the cervix without evidence of disease;
3. Adequately treated papillary, noninvasive bladder cancer; or
4. Low-grade prostate cancer that is on active surveillance and not expected to
clinically progress over 2 years.
6. Patients who are on BBs and unable to switch therapy; Note: Patients on BBs who are
able to switch therapy will undergo a gradual tapering of their current BB under the
guidance of the Investigator. At the Investigator's discretion, the initial days of
propranolol administration may be permitted to overlap with the final days of
tapering of the previous BB. Patients may not be treated with cardiovascular drugs
that would interact with propranolol including angiotensin-converting enzyme (ACE)
inhibitors, calcium channel blockers, and alpha blockers at study enrollment and
while on propranolol during the study.
7. Patients with severe asthma who require beta agonist therapy;
8. History of poor and uncontrolled cardiovascular or pulmonary disease such as
myocardial infarction, cardiac arrhythmias, transient ischemic attack, congestive
heart failure (New York Heart Association heart failure class >2), stroke,
unexplained syncope, or chronic obstructive pulmonary disease;
9. History of long QT syndrome or torsade de pointes;
10. Patients with a QTcF >470 msec or PR interval >280 msec on Screening 12-lead
electrocardiogram (ECG);
11. Active infection requiring treatment in the 7 days before Day 1;
12. Positive polymerase chain reaction test from nasal specimen for SARS-CoV-2 within 7
days prior to Day 1;
13. Pregnant or breastfeeding;
14. Known psychiatric or substance abuse disorder that would interfere with Protocol
compliance;
15. Receipt of any other investigational drug or device within 1 month before Day 1; or
16. Receipt of prior treatment with CXCR4 inhibitor for stem cell collection.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Diego (UCSD) - Moores Cancer Center
Address:
City:
La Jolla
Zip:
92037
Country:
United States
Status:
Recruiting
Contact:
Last name:
Trung Tran
Phone:
858-246-0682
Email:
tvtran@health.ucsd.edu
Facility:
Name:
University of Florida (UF) - Shands Cancer Center
Address:
City:
Gainesville
Zip:
32608
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jamie Knapp
Phone:
352-294-8970
Email:
jamidy00@ufl.edu
Facility:
Name:
Indiana Blood and Marrow Transplantation
Address:
City:
Indianapolis
Zip:
46077
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brooke Lucas
Phone:
317-528-7398
Email:
Brooke.Lucas@franciscanalliance.org
Facility:
Name:
University of Massachusetts
Address:
City:
Worcester
Zip:
01655
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alexandra Agrillo
Phone:
774-455-4456
Email:
Alexandra.Agrillo@umassmed.edu
Investigator:
Last name:
Muthalagu Ramanathan, MD
Email:
Principal Investigator
Facility:
Name:
Barbara Ann Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Grace Bae
Phone:
313-576-8030
Email:
baeg@karmanos.org
Facility:
Name:
John Theurer Cancer Center At Hackensack UMC
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew McConnell
Phone:
551-996-5949
Email:
Andrew.McConnell@hmhn.org
Facility:
Name:
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Contact:
Last name:
Khayla Leiva
Phone:
201-966-2214
Email:
leivak@mskcc.org
Facility:
Name:
The Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kate Caputo
Phone:
216-444-2558
Email:
CAPUTOK2@ccf.org
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jessica Aguilera
Phone:
713-745-9896
Email:
JMAguilera@mdanderson.org
Facility:
Name:
Virginia Commonwealth University - Massey Cancer Center
Address:
City:
Richmond
Zip:
23284
Country:
United States
Status:
Recruiting
Contact:
Last name:
Charles Hall
Phone:
804-628-5373
Email:
hallce3@vcu.edu
Start date:
February 13, 2023
Completion date:
June 30, 2025
Lead sponsor:
Agency:
GPCR Therapeutics, Inc.
Agency class:
Industry
Source:
GPCR Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05561751
