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.
Sex: All, ages: 18 Years to 75 Years
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:
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 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.
Participant flow
| Milestone | TG-0054 (3.14 mg/kg TG-0054 Administrated Via 15-min IV Infus) |
|---|
| Started | 12 |
| Completed | 12 |
| Not completed | 0 |
Outcome results
- Number of Patients Achieving the CD34+ Hematopoietic Stem Cell (HSC) Mobilization Target of ≧2.5×1000000 Cells/kg (Primary), Number, participants: TG-0054 (3.14 mg/kg) 7; TG-0054 (3.14 mg/kg)+G-CSF 5
- the Average Number of Leukapheresis Sessions (Secondary), Mean, number of leukapheresis sessions: TG-0054 (3.14 mg/kg) 2.0 +/- 0.82; TG-0054 (3.14 mg/kg)+G-CSF 1.4 +/- 0.55
- Circulating CD34+ Cell Count in Peripheral Blood (Secondary), Median, cells/kg: TG-0054 (3.14 mg/kg) 6000000 (4000000 to 10000000); TG-0054 (3.14 mg/kg)+G-CSF 5000000 (4000000 to 21000000)
Adverse events
Time frame: 9 months, from 23-Oct-2012 to 09-Jul-2013
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion) | 0 | 0/12 (0.0%) | 10/12 (83.3%) |
Other adverse events by term
| Term | Organ system | TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion) |
|---|
| Diarrhoea | Gastrointestinal disorders | 4/12 |
| Abdominal pain | Gastrointestinal disorders | 2/12 |
| Nausea | Gastrointestinal disorders | 2/12 |
| Paraesthesia oral | Gastrointestinal disorders | 2/12 |
| Blood pressure increased | Investigations | 2/12 |
| Haemoglobin decreased | Investigations | 2/12 |
| Platelet count decreased | Investigations | 2/12 |
| Neuropathy peripheral | Nervous system disorders | 4/12 |
| Paraesthesia | Nervous system disorders | 2/12 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2/12 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1/12 |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | 1/12 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 1/12 |
| Anaemia | Blood and lymphatic system disorders | 1/12 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1/12 |
| Chest discomfort | General disorders | 1/12 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1/12 |
| Pregnancy | Pregnancy, puerperium and perinatal conditions | 1/12 |