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

NCT01204164 | Completed Phase 1

• 1 other identifier: TG02-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

AML; ALL; Blast Crisis; MDS; Multiple Myeloma

Keywords

AML; ALL; MDS; CML in blast crisis; Multiple Myeloma; Carfilzomib refractory

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

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

  28 days

Secondary Outcomes (8)

• Safety

  28 days

• Pharmacokinetics of TG02

  28 days

• Clinical Benefit Response

  28 days

• Overall Response Rate

  28 days

• Progression-Free Survival

  28 days

Study Arms (4)

TG02 in AL

EXPERIMENTAL

Single agent TG02 citrate in acute leukemia patients

Drug: TG02 citrate

TG02 in MM

EXPERIMENTAL

Single Agent TG02 citrate in multiple myeloma patients

Drug: TG02 citrate

TG02 + CFZ in MM

EXPERIMENTAL

TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients

Drug: TG02 citrate; Drug: Carfilzomib

TG02 + CFZ + DEX in CFZ refractory MM

EXPERIMENTAL

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

Drug: TG02 citrate; Drug: Carfilzomib; Drug: Dexamethasone

Interventions

TG02 citrate DRUG

TG02 citrate capsules given orally.

Also known as: No other names.

TG02 + CFZ + DEX in CFZ refractory MM; TG02 + CFZ in MM; TG02 in AL; TG02 in MM

Carfilzomib DRUG

Carfilzomib per PI

Also known as: Kyprolis

TG02 + CFZ + DEX in CFZ refractory MM; TG02 + CFZ in MM

Dexamethasone DRUG

Dexamethasone (Oral or IV)

Also known as: Ozurdex, Maxidex, Decadron, Baycadron

TG02 + CFZ + DEX in CFZ refractory MM

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed AML, ALL, CML in blast crisis, or MDS
• + 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Tragara Pharmaceuticals, Inc.: lead

Study Sites (9)

RMCC

Denver, Colorado, 80218, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Rush

Chicago, Illinois, 60612, United States

Location

IU

Indianapolis, Indiana, 46202, United States

Location

HUMC

Hackensack, New Jersey, 07601, United States

Location

Cornell

New York, New York, 10021, United States

Location

OSU

Columbus, Ohio, 43210, United States

Location

SCRI

Nashville, Tennessee, 37203, United States

Location

MDACC

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Blast Crisis; Multiple Myeloma

Interventions

carfilzomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• T Parrott

  Tragara Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2010
• First Posted: September 17, 2010
• Study Start: August 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 6, 2016

Record last verified: 2016-05

Locations

US (9)