Safety and PK/PD of TG-0054 in Multiple Myeloma, Non-Hodgkin Lymphoma and Hodgkin Disease Patients

Phase 2

Completed

Conditions: Multiple Myeloma
Non-Hodgkin Lymphoma
Hodgkin Disease

Interventions: Drug: TG-0054 (2.24 mg/kg)
Drug: TG-0054 (3.14 mg/kg)

Registration Number: NCT01018979

Lead Sponsor: GPCR Therapeutics, Inc.

Brief Summary: A phase II study to evaluate the safety, pharmacokinetics, and hematopoietic stem cell mobilization of TG-0054 in patients with multiple myeloma, non-Hodgkin lymphoma or Hodgkin disease.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Male or female 18 to 70 years of age inclusive
Patients with confirmed pathology diagnosis of MM, NHL or HD
Potential candidate for autologous stem cell transplantation at Investigator's discretion
≦ 2 prior regimens of cytotoxic chemotherapy (rituximab, thalidomide, and bortezomib will not be considered as cytotoxic chemotherapy)
> 4 weeks since last cycle of chemotherapy prior to the study drug administration
Total dose of melphalan received ≦ 200 mg in the most recent chemotherapy treatment
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Recovered from all acute toxic effects of prior chemotherapy at Investigator's discretion
White blood cell (WBC) count ≧ 3.0 x 109/L on screening laboratory assessments
Absolute neutrophil count ≧ 1.5 x 109/L on screening laboratory assessments
Platelet count ≧ 100 x 109/L on screening laboratory assessments
Serum creatinine ≦ 2.2 mg/dL on screening laboratory assessments
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin < 2 x upper limit of normal (ULN) on screening laboratory assessments
Negative for human immunodeficiency virus (HIV)
Adequate cardiac and pulmonary function to undergo leukapheresis at Investigator's discretion
For females, one of the following criteria must be fulfilled:
1. At least one year post-menopausal, or
2. Surgically sterile, or
3. Willing to use a double-barrier method [intrauterine device (IUD) plus condom, spermicidal gel plus condom] of contraception throughout the study
Males must be willing to use a reliable form of contraception (use of a condom or a partner fulfilling the above criteria) from study Day 1 until 28 days after the last dose of TG-0054
Able to provide the signed informed consent

Exclusion Criteria

Received radiation therapy around the pelvic or spinal area within 6 months prior to the study drug administration
>10% bone marrow involvement of lymphoma in NHL patients
Failed previous stem cell collection [failed to collect 2 x 106 CD34+ cells/kg within 4 apheresis sessions after receiving granulocyte colony-stimulating factor (G-CSF)]
Patients who have undergone previous stem cell transplantation procedure
Received G-CSF within 2 weeks prior to the study drug administration
History of other cancer within the past 5 years excluding MM, NHL, HD, basal cell or squamous cell carcinoma of the skin
History of other hematologic disorders including bleeding or thromboembolic disease
History of poor and uncontrollable cardiovascular or pulmonary disease such as myocardial infarction, cardiac arrhythmias, transient ischemic attack, stroke or Chronic Obstructive Pulmonary Disease (COPD) patients hospitalized more than two times a year due to underlying disease
Diagnosis of sickle cell anemia or documented sickle cell trait
Uncontrollable malignancy with MM, NHL or HD, or carcinomatous meningitis, at Investigator's discretion
Any infection required antibiotic treatment or unexplained fever above 38 °C within 3 days prior to dosing
Pregnant or breast-feeding
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Received any other investigational drug within 1 month before entering the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TG-0054 (2.24 mg/kg)	TG-0054 (2.24 mg/kg)	TG-0054: 2.24 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of six leukapheresis sessions)
TG-0054 (3.14 mg/kg)	TG-0054 (3.14 mg/kg)	TG-0054: 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of six leukapheresis sessions)

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Achieved Mobilization Success of Hematopoietic Stem Cells in Patients With Multiple Myeloma (MM), Non-Hodgkin Lymphoma (NHL) or Hodgkin Disease (HD).	1 week	Patients who met the target CD34+ cell collection of ≧2 x 106 cells/kg after two apheresis sessions were classified as achieving mobilization success.

Secondary Outcome Measures

Name	Time	Method
Fold Increase of Circulating CD34+ Cell Counts in Peripheral Blood.	Baseline, 3 hours and 6 hours after infusion
Time at Which Maximum Plasma Concentration is Observed (Tmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Terminal Elimination Half-life (t1/2) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Terminal Elimination Rate Constant (λz) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
The Area Under the Plasma Concentration Time Curve (AUC) From 0 Hours to Infinity of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Clearance (CL) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Volume of Distribution at the Terminal State (Vz) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Maximum Plasma Concentration (Cmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
The Area Under the Plasma Concentration Time Curve (AUC) From 0 Hours to Time t of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Volume of Distribution at Steady State (Vss) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	36 hrs after infusion	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.
Circulating CD34+ Cell Counts in Peripheral Blood.	Baseline, 3 hours and 6 hours after infusion

Trial Locations

Locations (6): Buddist Tzu Chi General Hospital
🇨🇳
Hualien, Taiwan
Chang-Gung Memorial Hospital Chiayi
🇨🇳
Chiayi, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳
Taipei, Taiwan
Chang-Gung Memorial Hospital Linkou
🇨🇳
Linkou, Taiwan
Kaohsiung Medical University Hospital
🇨🇳
Kaohsiung, Taiwan