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

Sponsor

Tragara Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01699152

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Drug: TG02 citrate	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: TG02 citrate

TG02 citrate capsules given orally.

Drug: TG02 citrate

TG02 citrate capsules

Other Names:

No other names

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose [28 days]
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.

Secondary Outcome Measures

Adverse Events [28 days]
The number of patients with adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Progressive disease or marked splenomegaly and/or lymphadenopathy.
Anemia (hemoglobin <11 mg/dL) or thrombocytopenia (platelets<100,000/μL).
Unexplained weight loss exceeding 10% of body weight over the previous 6 months.
CTCAE Grade 2 or 3 fatigue.
Fevers >100.5º F or night sweats for more than 2 weeks without evidence of infection.
Progressive lymphocytosis, with an increase exceeding 50% over a 2 month period or a doubling time of less than 6 months.
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 ≤

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GRU	Augusta	Georgia	United States	30912
2	DFCI	Boston	Massachusetts	United States	02215
3	OSU	Columbus	Ohio	United States	43210
4	SCRI	Nashville	Tennessee	United States	37203
5	MDACC	Houston	Texas	United States	77030