Phase I Study of TG02 Citrate in Patients With Advanced Hematological Malignancies (TG02-101)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Tragara Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Tragara Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01204164
First received: September 14, 2010
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

This is a open-label, dose escalation study.


Condition Intervention Phase
AML
ALL
Blast Crisis
MDS
Multiple Myeloma
Drug: TG02 citrate
Drug: Carfilzomib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Advanced Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Tragara Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    To assess number of patients with dose-limiting toxicities


Secondary Outcome Measures:
  • Safety [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    To assess the number of participants with Adverse Events as a measure of safety

  • Pharmacokinetics [ Time Frame: 8 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: August 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TG02 citrate in leukemia
Single agent TG02 citrate in leukemia patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Experimental: TG02 citrate in multiple myeloma
Single Agent TG02 citrate in multiple myeloma patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Experimental: TG02 in combination with carfilzomib
TG02 in combination with carfilzomib in multiple myeloma patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Drug: Carfilzomib
Carfilzomib per PI
Other Name: Kyprolis

Detailed Description:

This is a multicenter, open-label, dose escalation study. The primary objective is to determine the highest dose of TG02 citrate that can safely be given to patients with different types of hematological malignancy.

This study consists of three parts: Part 1 - single agent TG02 in acute leukemia patients, Part 2 - single agent TG02 in multiple myeloma patients and Part 3 - TG02 in combination with carfilzomib in multiple myeloma patients.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Part 1 Inclusion Criteria:

  • Patients with the following histologically confirmed relapsed hematological malignancies for whom no curative treatment or standard therapy that conveys clinical benefit is available: Acute myelogenous leukemia (AML), Acute lymphocytic leukemia (ALL), Chronic myelogenous leukemia (CML) currently in blast crisis (defined as ≥30% blasts in bone marrow), High-risk myelodysplasia (MDS)
  • Patients (65 y/o or older) with AML who are not eligible for standard frontline chemo or who refuse treatment with intensive therapy.
  • Interval from prior treatment to time of study drug administration should be at least 5 half-lives for cytotoxic and noncytotoxic agents.
  • Persistent clinically significant toxicities from prior chemo must be ≤Grade 1
  • ECOG PS of 0, 1, or 2
  • Lab values within the following ranges:

    • Creatinine ≤2 X the upper limit of normal (ULN)
    • ALT and/or AST ≤2.5 X the ULN
    • Total bilirubin ≤1.5 X the ULN, unless considered due to Gilbert's syndrome
  • Negative serum or urine pregnancy test
  • Ability to take oral medication.

Part 2 Inclusion Criteria:

  • Relapsed multiple myeloma. Received at least ≥1 line of therapy, must have progressed after ≥1 prior therapy, and be patients for whom no standard therapy is available, or who decline such options. Prior autologous and/or allogeneic transplant is permitted.
  • Measurable disease defined as at least one of the following:

    • Serum monoclonal protein (M protein) ≥500 mg/dL
    • Urine monoclonal protein ≥200 mg per 24 hours
    • Involved free light chain level ≥10 mg/dL (≥100 mg/L) and an abnormal free light chain ratio in serum (<0.26 or >1.65)
    • Measurable soft tissue (not bone) plasmacytoma
  • Persistent clinically significant toxicities from prior chemo must be ≤Grade 1.
  • ECOG PS of 0, 1, or 2
  • Lab values within the following ranges:

    • ANC of >1000/mm3
    • Platelet count of ≥50,000/mm3
    • Cr ≤2 X the ULN
    • ALT and/or AST ≤2.5 X the ULN
    • Total bilirubin ≤1.5 X the ULN, unless considered due to Gilbert's syndrome
  • Negative serum or urine pregnancy test
  • Ability to take oral medication.

Part 3 Inclusion Criteria:

  • Measurable disease (within 14 days prior to enrollment) defined as at least one of the following:

    • Serum monoclonal protein (M protein) ≥500 mg/dL
    • Urine monoclonal protein ≥200 mg per 24 hours
    • Involved free light chain level ≥10 mg/dL (≥100 mg/L) and an abnormal free light chain ratio in serum (<0.26 or >1.65)
  • Meet at least one of the criteria below:

    • a. Received ≥2 prior therapies including a proteasome inhibitor and an immunomodulatory agent (IMiD). Prior carfilzomib and/or pomalidomide allowed.
    • b. Received ≥1 prior therapy and at least one of the following cytogenetic abnormalities as detected by FISH or cytogenetic analysis: 17p deletions and/or p53 abnormalities, 1q amplification, 1p deletion, or t(4;14) translocation.
  • Interval from prior treatment to time of study drug administration should be at least 5 half-lives or 3 weeks, which ever is shorter, for noncytotoxic agents.
  • Persistent clinically significant toxicities from prior chemo must be ≤Grade 1, or Grade 2 neuropathy without pain.

    -≥18 years of age

  • ECOG PS of 0, 1, or 2
  • Lab values within the following ranges:

    • ANC of >1000/mm3 independent of G-CSF
    • Platelet count of ≥50,000/mm3 independent of transfusion
    • MDRD calculated or measured CrCl of ≥30 mL/min
    • ALT and/or AST ≤3X the ULN
    • Total bilirubin ≤2X the ULN, unless considered due to Gilbert's syndrome
  • Negative serum or urine pregnancy test
  • Ability to take oral medication.

Parts 1 and 2 Exclusion Criteria:

  • Previous allogenic hematopoietic transplant within 90 days of study enrollment.
  • Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, HTN, CAD, CHF) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
  • Prolonged QTC interval of >450ms
  • Symptomatic CNS metastases. Patients with asymptomatic CNS disease may receive standard intrathecal chemo prior to enrollment and continue once dosed with study drug.
  • Known HIV or AIDS.
  • Being actively treated for a second malignancy.
  • Pregnant or nursing women.

Part 3 Exclusion Criteria:

  • Multiple myeloma of IgM subtype, POEMS syndrome, plasma cell leukemia
  • Corticosteroids (prednisone >10mg/ day or equivalent) must be discontinued ≥7 days of initiating therapy
  • Previous chemo within 2 weeks of first dose
  • History of ventricular arrhythmia or symptomatic conduction abnormality within 12 months
  • Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, and myocardial infarction within 6 months prior to first dose.
  • Screening ECG with a prolonged QTc interval (males: >450ms; females: >470ms)
  • Previous allogeneic hematopoietic transplant within 90 days of study enrollment. No active graft versus host disease (GVHD) requiring treatment.
  • Concurrent severe or uncontrolled medical disease (e.g., active systemic infection, diabetes, hypertension, coronary artery disease) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
  • Symptomatic CNS metastases. Patients with asymptomatic CNS disease may receive standard intrathecal chemotherapy prior to enrollment and continue once dosed with study drug.
  • Known HIV or AIDS.
  • Prior or second malignancy, except non-melanoma skin cancer, completely resected cervical or prostate cancer (with PSA of less than or equal to 0.1 ng/ml), or other cancer for which the subject has received curative therapy at least 3 years prior to study entry.
  • Treatment-related MDS
  • Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of first dose
  • Primary amyloid light-chain (AL) amyloidosis
  • Pleural effusions requiring thoracentesis or ascites requiring paracentesis
  • Pregnant or nursing women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204164

Contacts
Contact: M Syto 760-208-6916 msyto@tragarapharma.com

Locations
United States, Colorado
RMCC Completed
Denver, Colorado, United States, 80218
United States, Georgia
Emory Completed
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush Completed
Chicago, Illinois, United States, 60612
United States, Indiana
IU Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Mary Cangany    317-274-2178    mcangany@iupui.edu   
United States, New Jersey
HUMC Recruiting
Hackensack, New Jersey, United States, 07601
Contact: JTCC Research    551-996-5830    JTCCResearch@humed.com   
United States, New York
Cornell Completed
New York City, New York, United States, 10021
United States, Ohio
OSU Recruiting
Columbus, Ohio, United States, 43210
Contact: Cassidy Clark    614-688-8821    Cassidy.Clark@osumc.edu   
United States, Tennessee
SCRI Recruiting
Nashville, Tennessee, United States, 37203
Contact: SCRI patient info line    615-329-7274      
United States, Texas
MDACC Completed
Houston, Texas, United States, 77030
Sponsors and Collaborators
Tragara Pharmaceuticals, Inc.
Investigators
Study Director: M Syto Tragara Pharmaceuticals
  More Information

No publications provided

Responsible Party: Tragara Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01204164     History of Changes
Other Study ID Numbers: TG02-101
Study First Received: September 14, 2010
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Tragara Pharmaceuticals, Inc.:
AML
ALL
MDS
CML in blast crisis
Multiple Myeloma

Additional relevant MeSH terms:
Blast Crisis
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Bone Marrow Diseases
Carcinogenesis
Cardiovascular Diseases
Cell Transformation, Neoplastic
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplastic Processes
Paraproteinemias
Pathologic Processes
Vascular Diseases
Citric Acid
Anticoagulants
Chelating Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 23, 2014