Hodgkin Disease, Multiple Myeloma, Non-Hodgkin Lymphoma
Conditions
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.
Interventions
DRUGTG-0054 combined with G-CSF
Sponsors
GPCR Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 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 \[failed to collect 2.0\*10\^6 CD34+ cells/kg within 4 leukapheresis sessions after receiving granulocyte colony-stimulating factor (G-CSF)\]; * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 5 to Day 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 5 to Day 8 | 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. |
| Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Day 5 to Day 9 | 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. |
| the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) to Day 6 (2nd leukapheresis session) | determine circulating CD34+ cell counts in peripheral blood |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TG-0054 Combined With G-CSF 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. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | TG-0054 Combined With G-CSF |
|---|---|
| Age, Continuous | 58 years |
| BMI | 29.3 kg/m^2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 8 Participants |
| Weight | 82.4 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 6 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Day 5 to Day 8
Population: There were total 9 MM patients and 3 NHL or HD patients . A MM patient was treated with Revlimid, Following 2 leukapheresis sessions, a cumulative total of 0.18 x 10\^6 cells/kg were collected. PI and Medical Monitor didn't feel that further leukapheresis sessions would achieve more cells, so the patient didn't have additional sessions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Within 1 Leukapheresis Session | 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 | Multiple Myeloma | 0.6667 Proportion of participants |
| Within 1 Leukapheresis Session | 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 | Overall | 0.50000 Proportion of participants |
| Within 1 Leukapheresis Session | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of participants |
| Within 2 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of participants |
| Within 2 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of participants |
| Within 2 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of participants |
| Within 3 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of participants |
| Within 3 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of participants |
| Within 3 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of participants |
| Within 4 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of participants |
| Within 4 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of participants |
| Within 4 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of participants |
Secondary
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.
Time frame: Day 5 to Day 8
Population: There were total 9 MM patients and 3 NHL or HD patients . A MM patient was treated with Revlimid, Following 2 leukapheresis sessions, a cumulative total of 0.18 x 10\^6 cells/kg were collected. PI and Medical Monitor didn't feel that further leukapheresis sessions would achieve more cells, so the patient didn't have additional sessions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Within 1 Leukapheresis Session | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of patients |
| Within 1 Leukapheresis Session | 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 | Multiple Myeloma | 0.8889 Proportion of patients |
| Within 1 Leukapheresis Session | 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 | Overall | 0.9167 Proportion of patients |
| Within 2 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of patients |
| Within 2 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of patients |
| Within 2 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of patients |
| Within 3 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of patients |
| Within 3 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of patients |
| Within 3 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of patients |
| Within 4 Leukapheresis Sessions | 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 | Non-Hodgkin Lymphoma or Hodgkin Disease | 1.0000 Proportion of patients |
| Within 4 Leukapheresis Sessions | 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 | Overall | 0.9167 Proportion of patients |
| Within 4 Leukapheresis Sessions | 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 | Multiple Myeloma | 0.8889 Proportion of patients |
Secondary
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.
Time frame: Day 5 to Day 9
Population: There were total 9 MM patients and 3 NHL or HD patients . A MM patient was treated with Revlimid, Following 2 leukapheresis sessions, a cumulative total of 0.18 x 10\^6 cells/kg were collected. PI and Medical Monitor didn't feel that further leukapheresis sessions would achieve more cells, so the patient didn't have additional sessions.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Within 1 Leukapheresis Session | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Overall | 0.5000 Proportion of patients |
| Within 1 Leukapheresis Session | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of patients |
| Within 1 Leukapheresis Session | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Multiple myeloma | 0.6667 Proportion of patients |
| Within 2 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Multiple myeloma | 0.8889 Proportion of patients |
| Within 2 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Overall | 0.6667 Proportion of patients |
| Within 2 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of patients |
| Within 3 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Multiple myeloma | 0.8889 Proportion of patients |
| Within 3 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Overall | 0.6667 Proportion of patients |
| Within 3 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of patients |
| Within 4 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Overall | 0.6667 Proportion of patients |
| Within 4 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of patients |
| Within 4 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Multiple myeloma | 0.8889 Proportion of patients |
| Within 5 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Multiple myeloma | 0.8889 Proportion of patients |
| Within 5 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Overall | 0.6667 Proportion of patients |
| Within 5 Leukapheresis Sessions | Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions | Non-Hodgkin Lymphoma or Hodgkin Disease | 0.0000 Proportion of patients |
Secondary
the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF
determine circulating CD34+ cell counts in peripheral blood
Time frame: Day 5 (1st leukapheresis session) to Day 6 (2nd leukapheresis session)
Population: There were 5 patients who achived target number of CD34+ cells (\>=5.0\*10\^6 cells/kg) within two leukapheresis sessions and therefore didn't undergo addtional sessions. Among 7 patients who undergone 6 sessions, there were 1 patient didn't collect blood sample at 4h, 6h post-infusion and post-leukapheresis, and 1 patient 6h post-infusion not done.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Within 1 Leukapheresis Session | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) | 32.50 cells/µL |
| Within 1 Leukapheresis Session | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 6 (2nd leukapheresis session) | 16.00 cells/µL |
| Within 2 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) | 43.50 cells/µL |
| Within 2 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 6 (2nd leukapheresis session) | 28.00 cells/µL |
| Within 3 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 6 (2nd leukapheresis session) | 20.00 cells/µL |
| Within 3 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) | 42.00 cells/µL |
| Within 4 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 6 (2nd leukapheresis session) | 34.00 cells/µL |
| Within 4 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) | 60.50 cells/µL |
| Within 5 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 6 (2nd leukapheresis session) | 21.00 cells/µL |
| Within 5 Leukapheresis Sessions | the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF | Day 5 (1st leukapheresis session) | 35.50 cells/µL |