Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Advanced Hematological Malignancies
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 120
- Locations
- 9
- Primary Endpoint
- Maximum Tolerated Dose
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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
Arms & Interventions
TG02 in AL
Single agent TG02 citrate in acute leukemia patients
Intervention: TG02 citrate (Drug)
TG02 in MM
Single Agent TG02 citrate in multiple myeloma patients
Intervention: TG02 citrate (Drug)
TG02 + CFZ in MM
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
Intervention: TG02 citrate (Drug)
TG02 + CFZ in MM
TG02 in combination with carfilzomib and dexamethasone in multiple myeloma patients
Intervention: Carfilzomib (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
Intervention: TG02 citrate (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
Intervention: Carfilzomib (Drug)
TG02 + CFZ + DEX in CFZ refractory MM
TG02 in combination with carfilzomib and dexamethasone in carfilzomib refractory multiple myeloma patients
Intervention: Dexamethasone (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: 28 days
Maximum Tolerated Dose refers to the highest dose of TG02 administered that will produce the desired effect without unacceptable toxicity.
Secondary Outcomes
- Safety(28 days)
- Pharmacokinetics of TG02(28 days)
- Clinical Benefit Response(28 days)
- Overall Response Rate(28 days)
- Progression-Free Survival(28 days)
- Overall Survival(28 days)
- Duration of Response(28 days)
- Pharmacodynamics(28 days)