Phase 1 Study of TG02 Citrate in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Phase 1 Dose-Escalation and Pharmacokinetic Study of TG02 Citrate in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

This is a multi-center, open-label, dose escalation study.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: TG02 citrate

Detailed Description

The primary objective is to determine the highest dose of TG02 citrate that can be safely given to patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • GRU
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • DFCI
  • Ohio
    • Columbus, Ohio, United States, 43210
      • OSU
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI
  • Texas
    • Houston, Texas, United States, 77030
      • MDACC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma.

• Patients must meet one or more of the following indications for treatment:

  1. Progressive disease or marked splenomegaly and/or lymphadenopathy.
  2. Anemia (hemoglobin <11 mg/dL) or thrombocytopenia (platelets<100,000/μL).
  3. Unexplained weight loss exceeding 10% of body weight over the previous 6 months.
  4. CTCAE Grade 2 or 3 fatigue.
  5. Fevers >100.5º F or night sweats for more than 2 weeks without evidence of infection.
  6. Progressive lymphocytosis, with an increase exceeding 50% over a 2 month period or a doubling time of less than 6 months.
  7. Need for cytoreduction prior to allogeneic stem cell transplant.
• Patients must have relapsed or refractory disease after ≥1 prior line of treatment.
• The interval from prior treatment to time of study drug administration should be at least 5 half-lives for cytotoxic and noncytotoxic agents.
• Low-dose corticosteroids (prednisone <20 mg/ day or equivalent dose) are permitted throughout study.
• Clinically significant toxicities from prior chemotherapy must be resolved to Grade ≤ 1.
• Age >18 years.
• ECOG performance status ≤2.
• Life expectancy ≥ 12 weeks.

• Patients must have normal organ and marrow function as defined below:

  • absolute neutrophil count >1,000/μL in absence of bone marrow involvement
  • platelets ≥30,000/μL in absence of bone marrow involvement
  • If patient has extensive bone marrow involvement, minimum ANC and platelet levels are not required.
  • total bilirubin ≤1.5 X institutional ULN unless due to Gilbert's syndrome, controlled autoimmune hemolytic anemia or immune thrombocytopenia
  • AST(SGOT)/ALT(SGPT) <2.5 X institutional ULN unless due to disease
  • creatinine <2.0 mg/dL OR creatinine clearance >50 mL/min/1.73 m2
• Negative serum or urine pregnancy test at the time of first dose for WOCBP.
• Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for required assessments.
• Ability to take oral medication.

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (CTCAE Grade > 1) due to agents administered more than 3 weeks earlier.
• Patients who have received prior treatment with a CDK inhibitor within 12 months of study enrollment.
• High-dose corticosteroids (prednisone ≥20mg/day or equivalent dose) must be discontinued ≥ 7 days of initiating therapy.
• Patients with known central nervous system involvement.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition as TG02 citrate.
• Patients with G6PD deficiency.
• Concurrent severe or uncontrolled medical disease (including but not limited to history of ventricular arrhythmia or symptomatic conduction abnormality within 12 months, ongoing or active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) 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.
• Pregnant and/or breast-feeding women.
• Prior or second malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer for which the subject has received curative therapy at least 3 years prior to study entry.
• Known HIV or AIDs.
• QTc interval prolongation >450ms for males and >470 ms for females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TG02 citrate; TG02 citrate capsules given orally.	Drug: TG02 citrate; TG02 citrate capsules; Other Names: No other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose	To assess the number of patients with dose-limiting toxicities (DLT) and the dose of TG02 citrate that can be safely given to patients with CLL or SLL.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The number of patients with adverse events	28 days

Collaborators and Investigators

• Sponsor: Tragara Pharmaceuticals, Inc.
• Investigators: Study Director: T Parrott, Tragara Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: October 1, 2012
• First Submitted That Met QC Criteria: October 1, 2012
• First Posted (Estimate): October 3, 2012

Study Record Updates

• Last Update Posted (Actual): July 25, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: TG02-102