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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Hodgkin Disease; Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: TG-0054 (2.24 mg/kg); Drug: TG-0054 (3.14 mg/kg)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Chiayi, Taiwan
    • Chang-Gung Memorial Hospital ChiaYi
  • Hualien, Taiwan
    • Buddist Tzu Chi General Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Hospital
  • Linkou, Taiwan
    • Chang-Gung Memorial Hospital Linkou
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	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)
Experimental: 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)	Drug: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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.	Plasma concentrations of TG-0054 were determinate by validated LC-MS/MS method.	36 hrs after infusion
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
Terminal Elimination Rate Constant (λz) 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
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
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
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
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
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
Circulating CD34+ Cell Counts in Peripheral Blood.		Baseline, 3 hours and 6 hours after infusion

Collaborators and Investigators

• Sponsor: GPCR Therapeutics, Inc.
• Investigators: Principal Investigator: Tzeon-Jye Chiou, MD, Taipei Veterans General Hospital, Taiwan; Principal Investigator: Tso-Fu Wang, MD, Buddist Tzu Chi General Hospital; Principal Investigator: Sheng-Fung Lin, MD, Kaohsiung Medical University; Principal Investigator: Chih-Cheng Chen, MD, Chang-Gung Memorial Hospital ChiaYi; Principal Investigator: Po-Nan Wang, MD, Chang Gung memorial hospital; Principal Investigator: Jih-Luh Tang, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: November 24, 2009
• First Submitted That Met QC Criteria: November 24, 2009
• First Posted (Estimate): November 25, 2009

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: TG-0054-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No