Clinical trial NCT01018979: Safety and PK/PD of TG-0054 in Multiple Myeloma, Non-Hodgkin Lymphoma and Hodgkin Disease Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Non-Hodgkin Lymphoma
Hodgkin Disease
Lead sponsor: GPCR Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2009-11-25
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: 1 week
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Fold Increase of Circulating CD34+ Cell Counts in Peripheral Blood.
timeFrame: Baseline, 3 hours and 6 hours after infusion
measure: Time at Which Maximum Plasma Concentration is Observed (Tmax) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Terminal Elimination Half-life (t1/2) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Terminal Elimination Rate Constant (λz) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: 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.
timeFrame: 36 hrs after infusion
measure: 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.
timeFrame: 36 hrs after infusion
measure: Clearance (CL) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Volume of Distribution at the Terminal State (Vz) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Volume of Distribution at Steady State (Vss) of TG-0054 in 12 Consented Patients With MM, NHL or HD.
timeFrame: 36 hrs after infusion
measure: Circulating CD34+ Cell Counts in Peripheral Blood.
timeFrame: Baseline, 3 hours and 6 hours after infusion
Other outcomes:
Locations:
city: Chiayi
country: Taiwan
facility: Chang-Gung Memorial Hospital Chiayi
city: Hualien
country: Taiwan
facility: Buddist Tzu Chi General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Linkou
country: Taiwan
facility: Chang-Gung Memorial Hospital Linkou
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Tzeon-Jye Chiou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Buddist Tzu Chi General Hospital
name: Tso-Fu Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaohsiung Medical University
name: Sheng-Fung Lin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital, Chiayi
name: Chih-Cheng Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Po-Nan Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Jih-Luh Tang, MD
role: PRINCIPAL_INVESTIGATOR
References: