A Study to Evaluate the Safety, Pharmacokinetics, and Hematopoietic Stem Cell Mobilization of TG-0054 Alone or in Combination With G-CSF in Patients With Multiple Myeloma, Non-Hodgkin Lymphoma or Hodgkin Disease

Study Overview
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Brief Summary
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This Phase II study is to Evaluate the Safety, Pharmacokinetics, and Hematopoietic Stem Cell Mobilization of TG-0054 alone or in combination with G-CSF in Patients with Multiple Myeloma, Non-Hodgkin Lymphoma or Hodgkin Disease.

Conditions
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Multiple Myeloma, Non-hodgkin's Lymphoma, Hodgkin's Disease

Intervention / Treatment
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* Drug: TG-0054


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 to 75 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; 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 from study Day 1 until 28 days after the last dose of TG-0054; 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 to the pelvis; Received > 6 cycles of lenalidomide; Evidence of bone marrow involvement of lymphoma in NHL patients; Failed previous stem cell collection [failed to collect 2 x 106 CD34+ cells/kg within 4 leukapheresis 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 being treated with anti-coagulant; 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; Patients with proliferative retinopathy; 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; Received prior treatment with TG-0054 but withdrew early from this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving the CD34+ Hematopoietic Stem Cell (HSC) Mobilization Target of ≧2.5×1000000 Cells/kg | Patients were all with multiple myeloma (MM), Non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD). Number of patients who mobilized the targeted total number of CD34+ cells within a maximum of 4 leukapheresis sessions in study arm 1 and arm 3. Patients in arm 1 followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1. Patients in arm 3 followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Average Number of Leukapheresis Sessions | To determine the average number of leukapheresis sessions required to collect 2.5 x10^6 CD34+ cells/kg. | 1 week | 
| Circulating CD34+ Cell Count in Peripheral Blood | Calculate the median total CD34+ cell counts across all leukapheresis sessions following TG 0054 administration alone and in combination with G-CSF mobilization in order to evaluate the pharmacodynamics (PD) of TG-0054 by determining circulating CD34+ cell counts in peripheral blood. | pre-dose(-2 to 0 h),2, 4 and 6 hr after dosing. |