IRB Study Number 23-286
Status Recruiting
Institute Taussig Cancer Institute
Description
2.1 Primary Objective
To determine the proportion of patients that will achieve ≥2 × 106 CD34+ cells/kg in 2 leukapheresis sessions following treatment with GPC-100 and propranolol with and without G-CSF.
2.2 Secondary Objectives
• To assess safety and tolerability of GPC-100 and propranolol with and without G-CSF in the mobilization of patients with MM undergoing ASCT;
• To determine the proportion of patients that will achieve ≥4 × 106 CD34+ cells/kg in 2 leukapheresis sessions;
• To determine the proportion of patients that will achieve ≥2 × 106 CD34+ cells/kg in 1 leukapheresis session;
• To determine the proportion of patients that will achieve ≥4 × 106 CD34+ cells/kg in 1 leukapheresis session;
• To determine the average number of leukapheresis sessions required to collect ≥2 × 106 CD34+ cells/kg and ≥4 × 106 CD34+ cells/kg;
• To evaluate the pharmacodynamics (PD) following treatment with GPC-100 and propranolol with and without G-CSF by determining circulating CD34+ cell counts in peripheral blood;
• To evaluate the PD changes following treatment with GPC-100 and propranolol with and without G-CSF by determining levels of the chemokine CXCL12 in peripheral blood; and • To assess mean time to ANC and platelet count recovery after ASCT.
Inclusion Criteria
Male or female, ≥18 years of age;
Patients with diagnosis of MM per the International Myeloma Working Group criteria29;
Eligible for ASCT at the Investigator’s discretion;
>4 weeks since completion of last cycle of chemotherapy prior to Day 1;
Patient must be on first or second complete response or partial response;
Eastern Cooperative Oncology Group performance status of 0 or 1 (see Appendix C);
Systolic blood pressure (SBP) 100 – 160 mmHg inclusive, and diastolic blood pressure (DBP) 60 - 100 mmHg inclusive;
ANC ≥1.0 × 109/L on Screening laboratory assessments;
Platelet count ≥100 × 109/L on Screening laboratory assessments;
Creatinine clearance ≥30 ml/min, as calculated according to the Cockcroft-Gault formula;
Aspartate aminotransferase and alanine aminotransferase ≤2 × upper limit of normal (ULN) and total bilirubin ≤1.5 × ULN on Screening laboratory assessments;
Adequate cardiac (left ventricular ejection fraction [LVEF] ≥50%) and pulmonary function (room air O2 saturation value ≥92%);
For females, 1 of the following criteria must be fulfilled:
a. At least 1 year postmenopausal; or
b. 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.
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
Patients must be willing and able to provide signed informed consent.
Exclusion Criteria
≥25% of BM irradiated within 5 years prior to Day 1 (see Appendix D);
No more than one year of therapy administered prior to stem cell mobilization, per institution standards;
Patients who have undergone previous stem cell transplant;
Receipt of G-CSF within 2 weeks prior to Day 1;
History of another malignancy except for the following:
a. Adequately treated local basal cell or squamous cell carcinoma of the skin;
b. Adequately treated carcinoma in situ of the cervix without evidence of disease;
c. Adequately treated papillary, noninvasive bladder cancer; or
d. Low-grade prostate cancer that is on active surveillance and not expected to clinically progress over 2 years.
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.
Patients with severe asthma who require beta agonist therapy;
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;
Pulse/heart rate < 60 beats per minute;
History of long QT syndrome or torsade de pointes;
Patients with a QTcF >470 msec or PR interval >280 msec on Screening 12-lead electrocardiogram (ECG);
Active infection requiring treatment in the 7 days before Day 1;
Positive polymerase chain reaction test from nasal specimen for SARS-CoV-2 within 7 days prior to Day 1;
Pregnant or breastfeeding;
Known psychiatric or substance abuse disorder that would interfere with Protocol compliance;
Receipt of any other investigational drug or device within 1 month before Day 1; or
Receipt of prior treatment with CXCR4 inhibitor for stem cell collection.
