A Study 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

• Sponsor: GPCR Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01458288
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 9
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Non-hodgkin's Lymphoma; Hodgkin's Disease	Drug: TG-0054	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
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TG-0054 (3.14 mg/kg) TG-0054 (3.14 mg/kg)	Drug: TG-0054; 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of four leukapheresis sessions); Other Names: burixafor

Outcome Measures

Primary Outcome Measures

1. Number of Patients Achieving the CD34+ Hematopoietic Stem Cell (HSC) Mobilization Target of ≧2.5×1000000 Cells/kg [1 week]

   Patients were all with multiple myeloma (MM), Non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD). Number of patients who mobilized the targeted total number of CD34+ cells within a maximum of 4 leukapheresis sessions in study arm 1 and arm 3. Patients in arm 1 followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1. Patients in arm 3 followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8.

Secondary Outcome Measures

1. the Average Number of Leukapheresis Sessions [1 week]

   To determine the average number of leukapheresis sessions required to collect 2.5 x10^6 CD34+ cells/kg.

2. Circulating CD34+ Cell Count in Peripheral Blood [pre-dose(-2 to 0 h),2, 4 and 6 hr after dosing.]

   Calculate the median total CD34+ cell counts across all leukapheresis sessions following TG 0054 administration alone and in combination with G-CSF mobilization in order to evaluate the pharmacodynamics (PD) of TG-0054 by determining 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stony Brook University Hospital	Stony Brook	New York	United States	11794

Sponsors and Collaborators

• GPCR Therapeutics, Inc.

Investigators

• Principal Investigator: Michael W. Schuster, M.D., Stony Brook University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GPCR Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01458288
• Other Study ID Numbers: TG-0054-03
• First Posted: Oct 24, 2011
• 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

Recruitment Details	Duration of the Study: This study will consist of a 14-day screening period, a 2- to 11-day treatment period, and a 7-day follow-up period. Number of Patients: Approximately 12 treatment evaluable patients will be enrolled in this study. Study Location: Single site in US.

Arm/Group Title	TG-0054 (3.14 mg/kg TG-0054 Administrated Via 15-min IV Infus)
Arm/Group Description	TG-0054 (3.14 mg/kg) TG-0054: 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of four leukapheresis sessions)
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion)
Arm/Group Description	TG-0054 (3.14 mg/kg) TG-0054: 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of four leukapheresis sessions)
Overall Participants	12
Age, Customized (participants) [Number]
18 to 75 years old	12 100%
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Achieving the CD34+ Hematopoietic Stem Cell (HSC) Mobilization Target of ≧2.5×1000000 Cells/kg
Description	Patients were all with multiple myeloma (MM), Non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD). Number of patients who mobilized the targeted total number of CD34+ cells within a maximum of 4 leukapheresis sessions in study arm 1 and arm 3. Patients in arm 1 followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1. Patients in arm 3 followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG-0054 (3.14 mg/kg)	TG-0054 (3.14 mg/kg)+G-CSF
Arm/Group Description	Patients followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1.	Patients followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8.
Measure Participants	7	5
Number [participants]	7 58.3%	5 NaN

2. Secondary Outcome

Title	the Average Number of Leukapheresis Sessions
Description	To determine the average number of leukapheresis sessions required to collect 2.5 x10^6 CD34+ cells/kg.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG-0054 (3.14 mg/kg)	TG-0054 (3.14 mg/kg)+G-CSF
Arm/Group Description	Patients followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1.	Patients followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8.
Measure Participants	7	5
Mean (Standard Deviation) [number of leukapheresis sessions]	2.0 (0.82)	1.4 (0.55)

3. Secondary Outcome

Title	Circulating CD34+ Cell Count in Peripheral Blood
Description	Calculate the median total CD34+ cell counts across all leukapheresis sessions following TG 0054 administration alone and in combination with G-CSF mobilization in order to evaluate the pharmacodynamics (PD) of TG-0054 by determining circulating CD34+ cell counts in peripheral blood.
Time Frame	pre-dose(-2 to 0 h),2, 4 and 6 hr after dosing.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG-0054 (3.14 mg/kg)	TG-0054 (3.14 mg/kg)+G-CSF
Arm/Group Description	Patients followed administration of TG-0054 (3.14 mg/kg) alone and leukapheresis start from study day 1.	Patients followed administration of TG-0054 (3.14 mg/kg) combined with granulocyte colony-stimulating factor (G-CSF) and leukapheresis start from study day 8.
Measure Participants	7	5
Median (Full Range) [cells/kg]	6000000	5000000

Adverse Events

Time Frame	9 months, from 23-Oct-2012 to 09-Jul-2013
Arm/Group Title	TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion)
Arm/Group Description	TG-0054 (3.14 mg/kg) TG-0054: 3.14 mg/kg TG-0054 administrated via 15-min IV infusion(allow a maximum of four leukapheresis sessions)
All Cause Mortality
	TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion)
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	TG-0054 (3.14 mg/kg Administrated Via 15-min IV Infusion)
	Affected / at Risk (%)	# Events
Total	10/12 (83.3%)
Blood and lymphatic system disorders
Anaemia	1/12 (8.3%)
Thrombocytopenia	1/12 (8.3%)
Gastrointestinal disorders
Diarrhoea	4/12 (33.3%)
Abdominal pain	2/12 (16.7%)
Nausea	2/12 (16.7%)
Paraesthesia oral	2/12 (16.7%)
General disorders
Chest discomfort	1/12 (8.3%)
Investigations
Blood pressure increased	2/12 (16.7%)
Haemoglobin decreased	2/12 (16.7%)
Platelet count decreased	2/12 (16.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/12 (8.3%)
Nervous system disorders
Neuropathy peripheral	4/12 (33.3%)
Paraesthesia	2/12 (16.7%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	2/12 (16.7%)
Dyspnoea	1/12 (8.3%)
Nasal congestion	1/12 (8.3%)
Rhinorrhoea	1/12 (8.3%)

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.