PD and Safety of TG-0054 Combined With G-CSF in Multiple Myeloma, Non-Hodgkin Lymphoma and Hodgkin Disease Patients

Study Overview
=================
Brief Summary
-----------------
This is a phase II study to evaluate the efficacy and safety of TG-0054 combined with G-CSF in mobilizing hematopoietic stem cells in patients with multiple myeloma, non-Hodgkin lymphoma or Hodgkin disease.

Official Title
-----------------
A Phase II, Open-Label Study to Evaluate the Hematopoietic Stem Cell Mobilization of TG-0054 Combined With G-CSF in Patients With Multiple Myeloma, Non-Hodgkin Lymphoma or Hodgkin Disease

Conditions
-----------------
Multiple Myeloma, Non-Hodgkin Lymphoma, Hodgkin Disease

Intervention / Treatment
-----------------
* Drug: TG-0054 combined with G-CSF


Participation Criteria
=================
Eligibility Criteria
-----------------
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*10^9/L on screening laboratory assessments; Absolute neutrophil count ≧ 1.5*10^9/L on screening laboratory assessments; Platelet count ≧ 100*10^9/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 2.0*10^6 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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 combined with G-CSF<br>1. G-CSF: 10 μg/kg/day, administrated via SC injections from Day 1 to Day 8; 2. TG-0054: 3.14 mg/kg, administrated via 15-min IV infusion from Day 5 to Day 9 as needed to reach the target collection goal | Drug: TG-0054 combined with G-CSF<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients From Whom a Total Number of CD34+ Cells ≥5.0 x 10^6 Cells/kg Was Collected Within the First 4 Leukapheresis Sessions | The primary efficacy endpoint was the proportion of patients from whom a total number of CD34+ cells ≥5.0 x 10^6 cells/kg was collected within the first 4 leukapheresis sessions. For the primary efficacy endpoint, each patient's CD34+ cell number was calculated as the sum of CD34+ cell numbers collected from (up to) the first 4 leukapheresis sessions. | Day 5 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients From Whom a Total Number of CD34+ Cells ≥2.5 x 10^6 Cells/kg Was Collected Within the First 4 Leukapheresis Sessions | The secondary efficacy endpoint was the proportion of patients from whom a total number of CD34+ cells ≥2.5 x 10^6 cells/kg was collected within the first 4 leukapheresis sessions. Each patient's CD34+ cell number was calculated as the sum of CD34+ cell numbers collected from (up to) the first 4 leukapheresis sessions. | Day 5 to Day 8 | 
| Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | The secondary efficacy endpoint was the proportion of patients from whom a total number of CD34+ cells ≥6.0 x 10^6 cells/kg was collected within 5 leukapheresis sessions. Each patient's CD34+ cell number was calculated as the sum of CD34+ cell numbers collected from (up to) 5 leukapheresis sessions. | Day 5 to Day 9 | 
| the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | determine circulating CD34+ cell counts in peripheral blood | Day 5 (1st leukapheresis session) to Day 6 (2nd leukapheresis session) |