Phase 1B- Open Label Dose-Ranging Study of Oral AFX-2 in Adults With Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This trial will assess the tolerability and safety of AFX-2 over a range of five dose levels in adults with low-, intermediate- or high-risk Chronic Lymphocytic Leukemia (CLL). The trial will also determine the impact of dose on quality of life indices and on biological and immune responses, and will assess if there is a maximum tolerated dose and/or dose-limiting toxicity in this study population.

Official Title
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Phase 1B- Open Label Dose-Ranging Study of Oral AFX-2 in Adults With Chronic Lymphocytic Leukemia

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: AFX-2
* Drug: AFX-2
* Drug: AFX-2
* Drug: AFX-2
* Drug: AFX-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult men and women >18 years of age Diagnosis of CLL per NCI Working Group Criteria; with phenotypic evidence (i.e.. flow cytometry or bone marrow biopsy) of chronic lymphocytic leukemia (MEDDRA Code - 10008960; ICD-O3-9823) Disease meets criteria for low-risk (Rai Stage 0), intermediate-risk (Rai Stage I- II), or high-risk (Rai Stage III-IV) disease Life expectancy of ≥ 3 months at Screening. ECOG performance status 0-3 Laboratory parameters (taken < 14 days of Study Day 0): Hematologic parameters: Hemoglobin > 9 gm/dL (stable, not dropping); Absolute Granulocyte Count (AGC) > 1.0 x 109/L; Platelets > 50 x 109/L; not requiring immediate transfusion. Coagulation: PT/PTT/INR: ± 10% of NL for lab; INR: 1.0-1.43 BUN < 40; serum Creatinine ≤ 2.0 mg/dL, OR Creatinine Clearance > 90 mL/min/1.73m2 IF serum Creatinine > 2.0 mg/dL Liver function tests (AST, ALT, ALP, LDH): < 2.5 x institutional ULN; Total bilirubin: < 2.0 x institutional ULN Human Immunodeficiency Virus (HIV) negative Pregnancy test: negative urine pregnancy test for females of child-bearing potential, Free of disease from prior malignancy/ies for > 2 years, except for basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. If not surgically sterile, or post-menopausal (> 12 months with no menstrual flow), willing to practice birth control (barrier + contraception) throughout duration of study. Able and willing to swallow capsules. Willing to limit alcohol intake during the study treatment period. Willing to sign the informed consent. Exclusion Criteria: Lymphoproliferative disease other than CLL Prior use of the test article (AFX-2), or ginseng-containing products (American, Asian, etc.) ≤ 1 year prior to study entry. Known allergy to the test article or ginseng-containing products Active infection requiring systemic treatment Prior or current therapy: Splenectomy. Currently requiring anticoagulant therapy Requiring active treatment for B-CLL or ≤ 28 days post-treatment for B-CLL or other condition requiring: chemotherapy, radiation therapy, monoclonal antibodies, systemic steroids, antihistamines or non-steroidal anti-inflammatory drugs, including ibuprofen, indomethacin, COX-2 inhibitors etc. ≤ 10 days: non-steroidal hormonal therapy (other than for contraception or thyroid) ≤ 10 days: antibiotic prophylaxis History of therapy with immunological reagents, such as allogeneic bone marrow transplant, monoclonal antibody therapy, intravenous immunoglobulin, or hematopoietic stem cell transplantation. (Note: Immunotherapy for allergies is permitted as long as the last treatment was both (a) prior to the CLL diagnosis and (b) > 5 years prior to trial enrollment.) < 90 days post treatment with chlorambucil < 90 days post general anesthesia Uncontrolled intercurrent condition, including, but not limited to, cardiovascular, pulmonary, renal, hepatic, GI, GU, neurologic, metabolic, psychiatric, etc. Current or prior investigational product or procedure < 56 days preceding study entry (Baseline -Visit 2; Study Day 0). Unwilling to discontinue use of nonprescription (OTC), nutritional or dietary supplements during the study period (as further defined by protocol). Pregnant, lactating. Any condition, personal or social situation that precludes or limits the ability of the participant to provide informed consent or comply with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dose arm 1<br> | Drug: AFX-2<br>* Dose level 1<br>|
| Other: Dose arm 2<br> | Drug: AFX-2<br>* Dose level 2<br>|
| Other: Dose arm 3<br> | Drug: AFX-2<br>* Dose level 3<br>|
| Other: Dose arm 4<br> | Drug: AFX-2<br>* Dose level 4<br>|
| Other: Dose arm 5<br> | Drug: AFX-2<br>* Dose level 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability will be assessed based on the incidence, duration and intensity of adverse events | Adverse events will be graded according to NCI-CTC v4. | 0-8 weeks | 
| Safety and tolerability will also be determined by assessing any changes in study test results from baseline values | Study tests that will determine safety include vital signs, clinical laboratory tests (hematology, serum chemistries, coagulation, urinalysis) and 12-lead EKG | 1 week, 4 weeks, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life indices |  | 1 week, 4 weeks, 8 weeks | 
| Maximum tolerated dose and/or dose-limiting toxicity |  | 1 week, 4 weeks, 8 weeks | 
| Biological and immune responses |  | 1 week, 4 weeks, 8 weeks |