search
Back to results

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

Primary Purpose

AML, ALL, Blast Crisis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TG02 citrate
Carfilzomib
Dexamethasone
Sponsored by
Tragara Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AML focused on measuring AML, ALL, MDS, CML in blast crisis, Multiple Myeloma, Carfilzomib refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • RMCC
  • Emory
  • Rush
  • IU
  • HUMC
  • Cornell
  • OSU
  • SCRI
  • MDACC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

TG02 in AL

TG02 in MM

TG02 + CFZ in MM

TG02 + CFZ + DEX in CFZ refractory MM

Arm Description

Single agent TG02 citrate in acute leukemia patients

Single Agent TG02 citrate in multiple myeloma patients

TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients

TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose
Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.

Secondary Outcome Measures

Safety
Safety data will include vital signs, ECGs, PE findings, clinical laboratory parameters, ECOG PS, AEs/SAEs and concomitant medications.
Pharmacokinetics of TG02
Plasma will be analyzed to determine TG02 concentration.
Clinical Benefit Response
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
Overall Response Rate is defined as the sum of patients with sCR, CR, VGPR and PR.
Progression-Free Survival
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
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
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
Pharmacodynamic sampling may include whole blood and bone marrow at baseline and post-treatment for pathway determination if available.

Full Information

First Posted
September 14, 2010
Last Updated
May 5, 2016
Sponsor
Tragara Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT01204164
Brief Title
Phase 1 Study of TG02 Citrate in Patients With Advanced Hematological Malignancies
Acronym
TG02-101
Official Title
Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Advanced Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tragara Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AML, ALL, Blast Crisis, MDS, Multiple Myeloma
Keywords
AML, ALL, MDS, CML in blast crisis, Multiple Myeloma, Carfilzomib refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TG02 in AL
Arm Type
Experimental
Arm Description
Single agent TG02 citrate in acute leukemia patients
Arm Title
TG02 in MM
Arm Type
Experimental
Arm Description
Single Agent TG02 citrate in multiple myeloma patients
Arm Title
TG02 + CFZ in MM
Arm Type
Experimental
Arm Description
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
Arm Title
TG02 + CFZ + DEX in CFZ refractory MM
Arm Type
Experimental
Arm Description
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
Intervention Type
Drug
Intervention Name(s)
TG02 citrate
Other Intervention Name(s)
No other names.
Intervention Description
TG02 citrate capsules given orally.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis
Intervention Description
Carfilzomib per PI
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Ozurdex, Maxidex, Decadron, Baycadron
Intervention Description
Dexamethasone (Oral or IV)
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Safety
Description
Safety data will include vital signs, ECGs, PE findings, clinical laboratory parameters, ECOG PS, AEs/SAEs and concomitant medications.
Time Frame
28 days
Title
Pharmacokinetics of TG02
Description
Plasma will be analyzed to determine TG02 concentration.
Time Frame
28 days
Title
Clinical Benefit Response
Description
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).
Time Frame
28 days
Title
Overall Response Rate
Description
Overall Response Rate is defined as the sum of patients with sCR, CR, VGPR and PR.
Time Frame
28 days
Title
Progression-Free Survival
Description
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.
Time Frame
28 days
Title
Overall Survival
Description
Overall Survival is time to death, which is measured from the date of first study drug administration until the date of death.
Time Frame
28 days
Title
Duration of Response
Description
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.
Time Frame
28 days
Title
Pharmacodynamics
Description
Pharmacodynamic sampling may include whole blood and bone marrow at baseline and post-treatment for pathway determination if available.
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
T Parrott
Organizational Affiliation
Tragara Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
RMCC
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Emory
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
IU
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
HUMC
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Cornell
City
New York City
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
OSU
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MDACC
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Phase 1 Study of TG02 Citrate in Patients With Advanced Hematological Malignancies

We'll reach out to this number within 24 hrs