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

Multiple Myeloma Clinical Trial

Official title:

A Phase II, Open-Label, Multi-Center 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01018979
• Other study ID #: TG-0054-02
• Status: Completed
• Phase: Phase 2
• Start date: February 2010
• Est. completion date: October 2011

Study information

• Verified date: April 2021
• Source: GPCR Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Non-Hodgkin Lymphoma

Intervention

Drug:
• 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 administrated via 15-min IV infusion(allow a maximum of six leukapheresis sessions)

Locations

Country	Name	City	State
Taiwan	Chang-Gung Memorial Hospital Chiayi	Chiayi
Taiwan	Buddist Tzu Chi General Hospital	Hualien
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Chang-Gung Memorial Hospital Linkou	Linkou
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
GPCR Therapeutics, Inc.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Patients who met the target CD34+ cell collection of ?2 x 106 cells/kg after two apheresis sessions were classified as achieving mobilization success.	1 week
Secondary	Maximum Plasma Concentration (Cmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Fold Increase of Circulating CD34+ Cell Counts in Peripheral Blood.		Baseline, 3 hours and 6 hours after infusion
Secondary	Time at Which Maximum Plasma Concentration is Observed (Tmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Terminal Elimination Half-life (t1/2) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Terminal Elimination Rate Constant (?z) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	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.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	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.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Clearance (CL) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Volume of Distribution at the Terminal State (Vz) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Volume of Distribution at Steady State (Vss) of TG-0054 in 12 Consented Patients With MM, NHL or HD.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
Secondary	Circulating CD34+ Cell Counts in Peripheral Blood.		Baseline, 3 hours and 6 hours after infusion