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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Myeloma, Non-Hodgkin Lymphoma, Hodgkin Disease

Intervention / Treatment
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* Drug: TG-0054 (2.24 mg/kg)
* Drug: TG-0054 (3.14 mg/kg)


Participation Criteria
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Eligibility Criteria
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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: At least one year post-menopausal, or Surgically sterile, or 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TG-0054 (2.24 mg/kg)<br>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)<br>* TG-0054: 2.24 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of six leukapheresis sessions)<br>|
| Experimental: TG-0054 (3.14 mg/kg)<br>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)<br>* TG-0054: 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of six leukapheresis sessions)<br>|

What is the study measuring?
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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 |