Phase 1 Study of TG02 Citrate in Patients With Advanced Hematological Malignancies (TG02-101)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Tragara Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Tragara Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01204164
First received: September 14, 2010
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

This is a multicenter, open-label, dose escalation Phase 1 study.


Condition Intervention Phase
AML
ALL
Blast Crisis
MDS
Multiple Myeloma
Drug: TG02 citrate
Drug: Carfilzomib
Drug: Dexamethasone
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: Yes ]
    Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.


Secondary Outcome Measures:
  • Safety [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Safety data will include vital signs, ECGs, PE findings, clinical laboratory parameters, ECOG PS, AEs/SAEs and concomitant medications.

  • Pharmacokinetics of TG02 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Plasma will be analyzed to determine TG02 concentration.

  • Clinical Benefit Response [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Clinical Benefit Response is defined as the sum of all response categories for Overall Response Rate (ORR is defined as the sum of patients with sCR, CR, VGPR and PR) plus minimal response (MR).

  • Overall Response Rate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Overall Response Rate is defined as the sum of patients with sCR, CR, VGPR and PR.

  • Progression-Free Survival [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Progression-Free Survival is the time to disease progression or death, which is measured from the date of first study drug administration until the first date that recurrent or progressive disease is objectively documented or the date of death.

  • Overall Survival [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Overall Survival is time to death, which is measured from the date of first study drug administration until the date of death.

  • Duration of Response [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Duration of Response is the duration from first observation of response to the first documentation of disease progression, with deaths from causes other than disease progression censored. For the purposes of the calculation of the DOR, the date at which the response status was first observed rather than the date of confirmation is used as the start date.

  • Pharmacodynamics [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    Pharmacodynamic sampling may include whole blood and bone marrow at baseline and post-treatment for pathway determination if available.


Estimated Enrollment: 120
Study Start Date: August 2010
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TG02 in AL
Single agent TG02 citrate in acute leukemia patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Experimental: TG02 in MM
Single Agent TG02 citrate in multiple myeloma patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Experimental: TG02 + CFZ in MM
TG02 in combination with carfilzomib and dexamethasone 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
Experimental: TG02 + CFZ + DEX in CFZ refractory MM
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
Drug: TG02 citrate
TG02 citrate capsules given orally.
Other Name: No other names.
Drug: Carfilzomib
Carfilzomib per PI
Other Name: Kyprolis
Drug: Dexamethasone
Dexamethasone (Oral or IV)
Other Name: Ozurdex, Maxidex, Decadron, Baycadron

Detailed Description:

This is a multicenter, open-label, dose escalation, Phase 1/1b study.

For Parts 1, 2, and 3 of the 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.

For Part 4, the primary objective is to evaluate the safety and tolerability of once-weekly dosing at the maximum-tolerated dose/ Recommended Phase 2 Dose of TG02 in combination with carfilzomib.

This study consists of four parts:

  • Part 1: single agent TG02 in acute leukemia patients
  • Part 2: single agent TG02 in multiple myeloma patients
  • Part 3: TG02 in combination with carfilzomib in multiple myeloma patients
  • Part 4: TG02 in combination with carfilzomib in carfilzomib refractory 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:

  • Relapsed AML, ALL, CML in blast crisis, or MDS
  • 65+ yrs with AML not eligible for standard frontline chemo
  • Interval from prior treatment to time of study drug at least 5 half-lives for cytotoxic/ noncytotoxic agents.
  • Persistent clinically significant toxicities from prior chemo ≤ Grd 1
  • ECOG PS 0-2
  • Lab values:

    • Cr ≤ 2X ULN
    • ALT and/or AST ≤2.5 X ULN
    • Total bilirubin ≤1.5 X ULN unless considered due to Gilbert's syndrome
  • Negative pregnancy test
  • Can take oral med

Part 2 Inclusion Criteria:

  • Relapsed multiple myeloma. At least ≥1 line of therapy and progressed after ≥1 prior therapy
  • Measurable disease defined as at least one of the following:

    • Serum M ≥500 mg/dL
    • Urine M ≥200 mg per 24hr
    • Involved FLC ≥10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
    • Measurable soft tissue plasmacytoma
  • Persistent clinically significant toxicities from prior chemo ≤ Grd 1
  • ECOG PS 0-2
  • Lab values:

    • ANC of >1000/mm3
    • Platelets ≥50,000/mm3
    • Cr ≤2X the ULN
    • ALT and/or AST ≤2.5X ULN
    • Total bilirubin ≤1.5X ULN, unless considered due to Gilbert's syndrome
  • Negative pregnancy test
  • Can take oral med

Part 3 Inclusion Criteria:

  • Measurable disease defined as at least one of the following:

    • Serum M ≥500 mg/dL
    • Urine M protein ≥200 mg per 24hr
    • Involved FLC level ≥10 mg/dL and abnormal FLC ratio in serum (<0.26 or >1.65)
  • Meet at least one of the criteria below:

    • a. ≥2 prior therapies including proteasome inhibitor and immunomodulatory agent (IMiD)
    • b. ≥1 prior therapy and one of the following abnormalities: 17p del, p53, 1q amp, 1p del, t(4;14)
  • Interval from prior treatment to time of study drug at least 5 half-lives or 3 wks, which ever is shorter, for noncytotoxic agents
  • Persistent clinically significant toxicities from prior chemo ≤ Grd 1 or Grd 2 neuropathy without pain
  • ECOG PS 0-2
  • Lab values:

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

Part 4 Inclusion Criteria:

  • Measurable disease defined as at least one of the following:

    • Serum M ≥500 mg/dL
    • Urine M protein ≥200 mg per 24hr
    • Involved FLC level ≥10 mg/dL and an abnormal FLC ratio in serum (<0.26 or >1.65)
  • Received prior therapies including:

    • a. bortezomib
    • b. an IMiD
    • c. carfilzomib. Demonstrated disease progression on or within 60d of completion of carfilzomib therapy
  • Interval from prior treatment to time of study drug at least 5 half-lives or 3 wks, which ever is shorter, for noncytotoxic agents.
  • Persistent clinically significant toxicities from prior chemo ≤ Grd 1, or Grd 2 neuropathy without pain.
  • ECOG PS 0-2
  • Lab values:

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

Parts 1 and 2 Exclusion Criteria:

  • Previous allogenic hematopoietic transplant within 90 d
  • Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study
  • Prolonged QTC interval >450ms
  • Symptomatic CNS metastases
  • Known HIV or AIDS
  • Actively treated for a second malignancy
  • Pregnant or nursing women

Part 3 Exclusion Criteria:

  • Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
  • Corticosteroids discontinued ≥7 days of initiating therapy
  • Previous chemo within 2 wks
  • Hx of ventricular arrhythmia or symptomatic conduction abnormality within 12m
  • CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, myocardial infarction within 6m
  • Prolonged QTc interval (males >450ms, females >470ms)
  • Previous allogeneic hematopoietic transplant within 90 days of study enrollment, Active GVHD requiring treatment.
  • Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete the study
  • Symptomatic CNS metastases
  • Known HIV or AIDS
  • Prior or 2nd 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 yrs prior to study entry
  • Treatment-related MDS
  • Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
  • Primary AL amyloidosis
  • Pleural effusions requiring thoracentesis or ascites requiring paracentesis
  • Pregnant or nursing women

Part 4 Exclusion Criteria:

  • Multiple myeloma of IgM subtype, POEMS, plasma cell leukemia
  • Previous chemo within 2 wks
  • Hx ventricular arrhythmia or symptomatic conduction abnormality within 12m
  • CHF, symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, and myocardial infarction within 6m
  • Prolonged QTc interval (males >450ms, females >470ms)
  • Previous allogeneic hematopoietic transplant within 90 days. Active GVHD requiring treatment
  • Concurrent severe or uncontrolled medical disease that would compromise the safety or compromise the ability of the patient to complete study
  • Symptomatic CNS metastases
  • Known HIV or AIDS
  • Prior or 2nd 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 yrs prior to study entry
  • Treatment-related MDS
  • Significant neuropathy (Grd 3-4 or Grd 2 with pain) at the time of 1st dose
  • Primary 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: T Parrott 760-208-6919 tparrott@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: T Parrott 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: April 22, 2015
Health Authority: United States: Food and Drug Administration

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

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
BB 1101
Citric Acid
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 27, 2015