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

• Sponsor: GPCR Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02104427
• Collaborator: (none)
• Enrollment: 12
• Locations: 2
• Arm: 1
• Duration (Months): 9
• Patients Per Site: 6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Non-Hodgkin Lymphoma; Hodgkin Disease	Drug: TG-0054 combined with G-CSF	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stony Brook University Hospital	Stony Brook	New York	United States	11794
2	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203

Sponsors and Collaborators

• GPCR Therapeutics, Inc.

Investigators

• Principal Investigator: Michael M Schuster, MD, Stony Brook University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GPCR Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02104427
• Other Study ID Numbers: TG-0054-04
• First Posted: Apr 4, 2014
• Last Update Posted: Apr 19, 2021
• Last Verified: Apr 1, 2021

• Additional relevant MeSH terms: Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

Study Results

Participant Flow

Arm/Group Title	TG-0054 Combined With G-CSF
Arm/Group Description	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.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TG-0054 Combined With G-CSF
Arm/Group Description	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.
Overall Participants	12
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	4 33.3%
Male	8 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	1 8.3%
Black or African American	2 16.7%
White	8 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	82.4
BMI (kg/m^2) [Mean (Full Range) ]
Mean (Full Range) [kg/m^2]	29.3

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Within 1 Leukapheresis Session	Within 2 Leukapheresis Sessions	Within 3 Leukapheresis Sessions	Within 4 Leukapheresis Sessions
Arm/Group Description	Cumulative CD34+ cell counts ≥5.0 x 10^6 cells/kg within 1 leukapheresis session	Cumulative CD34+ cell counts ≥5.0 x 10^6 cells/kg within 2 leukapheresis session	Cumulative CD34+ cell counts ≥5.0 x 10^6 cells/kg within 3 leukapheresis session	Cumulative CD34+ cell counts ≥5.0 x 10^6 cells/kg within 4 leukapheresis session
Measure Participants	12	12	12	12
Overall	0.50000 4.2%	0.9167 NaN	0.9167 NaN	0.9167 NaN
Multiple Myeloma	0.6667 5.6%	0.8889 NaN	0.8889 NaN	0.8889 NaN
Non-Hodgkin Lymphoma or Hodgkin Disease	0.0000 0%	1.0000 NaN	1.0000 NaN	1.0000 NaN

2. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Within 1 Leukapheresis Session	Within 2 Leukapheresis Sessions	Within 3 Leukapheresis Sessions	Within 4 Leukapheresis Sessions
Arm/Group Description	Cumulative CD34+ cell counts ≥2.5 x 10^6 cells/kg within 1 leukapheresis session	Cumulative CD34+ cell counts ≥2.5 x 10^6 cells/kg within 2 leukapheresis session	Cumulative CD34+ cell counts ≥2.5 x 10^6 cells/kg within 3 leukapheresis session	Cumulative CD34+ cell counts ≥5.0 x 10^6 cells/kg within 4 leukapheresis session
Measure Participants	12	12	12	12
Overall	0.9167	0.9167	0.9167	0.9167
Multiple Myeloma	0.8889	0.8889	0.8889	0.8889
Non-Hodgkin Lymphoma or Hodgkin Disease	1.0000	1.0000	1.0000	1.0000

3. Secondary Outcome

Title	Proportion of Patients Who Mobilized the Targeted Total Number of CD34+ Cells (≥6.0 x 10^6 Cells/kg) Within 5 Leukapheresis Sessions
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Within 1 Leukapheresis Session	Within 2 Leukapheresis Sessions	Within 3 Leukapheresis Sessions	Within 4 Leukapheresis Sessions	Within 5 Leukapheresis Sessions
Arm/Group Description	Cumulative CD34+ cell counts ≥6.0 x 10^6 cells/kg within 1 leukapheresis session	Cumulative CD34+ cell counts ≥6.0 x 10^6 cells/kg within 2 leukapheresis session	Cumulative CD34+ cell counts ≥6.0 x 10^6 cells/kg within 3 leukapheresis session	Cumulative CD34+ cell counts ≥6.0 x 10^6 cells/kg within 4 leukapheresis session	Cumulative CD34+ cell counts ≥6.0 x 10^6 cells/kg within 5 leukapheresis session
Measure Participants	12	12	12	12	12
Overall	0.5000	0.6667	0.6667	0.6667	0.6667
Multiple myeloma	0.6667	0.8889	0.8889	0.8889	0.8889
Non-Hodgkin Lymphoma or Hodgkin Disease	0.0000	0.0000	0.0000	0.0000	0.0000

4. Secondary Outcome

Title	the Pharmacodynamics (PD) Following Treatment With TG-0054 When Combined With G-CSF
Description	determine circulating CD34+ cell counts in peripheral blood
Time Frame	Day 5 (1st leukapheresis session) to Day 6 (2nd leukapheresis session)

Outcome Measure Data

Analysis Population Description

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/Group Title	Pre-dose	4h Post-infusion	6h Post-infusion	Pre-leukapheresis	Post-leukapheresis
Arm/Group Description	Circulating CD34+ Cell Count (cells/µL) in Peripheral Blood at Pre-dose timepoint	Circulating CD34+ Cell Count (cells/µL) in Peripheral Blood at 4h post-infusion timepoint	Circulating CD34+ Cell Count (cells/µL) in Peripheral Blood at 6h post-infusion timepoint	Circulating CD34+ Cell Count (cells/µL) in Peripheral Blood at Pre-leukapheresis timepoint	Circulating CD34+ Cell Count (cells/µL) in Peripheral Blood at Post-leukapheresis timepoint
Measure Participants	12	12	12	12	12
Day 5 (1st leukapheresis session)	32.50	43.50	42.00	60.50	35.50
Day 6 (2nd leukapheresis session)	16.00	28.00	20.00	34.00	21.00

Adverse Events

Arm/Group Title	10 µg/kg/Day G-CSF Alone		10 µg/kg/Day G-CSF + 3.14 mg/kg TG-0054		Overall
Arm/Group Description	Days 1 through 4		Day 5 until end of study
All Cause Mortality
	10 µg/kg/Day G-CSF Alone		10 µg/kg/Day G-CSF + 3.14 mg/kg TG-0054		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	10 µg/kg/Day G-CSF Alone		10 µg/kg/Day G-CSF + 3.14 mg/kg TG-0054		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	10 µg/kg/Day G-CSF Alone		10 µg/kg/Day G-CSF + 3.14 mg/kg TG-0054		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		6/12 (50%)		7/12 (58.3%)
Gastrointestinal disorders
Diarrhoea	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Dry mouth	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Nausea	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
General disorders
Oedema peripheral	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Investigations
Platelet count decreased	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Metabolism and nutrition disorders
Hypocalcaemia	1/12 (8.3%)	1	0/12 (0%)	0	1/12 (8.3%)	1
Hypokalaemia	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Bone pain	2/12 (16.7%)	2	0/12 (0%)	0	2/12 (16.7%)	2
Nervous system disorders
Paraesthesia	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.