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

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.

Study Overview

• Status: Withdrawn
• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: AFX-2; Drug: AFX-2; Drug: AFX-2; Drug: AFX-2; Drug: AFX-2

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Jospeh Mercy Health System
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Cancer Center Of The Carolinas

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:

1. Adult men and women >18 years of age
2. 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)
3. Disease meets criteria for low-risk (Rai Stage 0), intermediate-risk (Rai Stage I- II), or high-risk (Rai Stage III-IV) disease
4. Life expectancy of ≥ 3 months at Screening.
5. ECOG performance status 0-3

6. 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,
7. 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.
8. If not surgically sterile, or post-menopausal (> 12 months with no menstrual flow), willing to practice birth control (barrier + contraception) throughout duration of study.
9. Able and willing to swallow capsules.
10. Willing to limit alcohol intake during the study treatment period.
11. Willing to sign the informed consent.

Exclusion Criteria:

1. Lymphoproliferative disease other than CLL
2. Prior use of the test article (AFX-2), or ginseng-containing products (American, Asian, etc.) ≤ 1 year prior to study entry.
3. Known allergy to the test article or ginseng-containing products
4. Active infection requiring systemic treatment

5. 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
6. Uncontrolled intercurrent condition, including, but not limited to, cardiovascular, pulmonary, renal, hepatic, GI, GU, neurologic, metabolic, psychiatric, etc.
7. Current or prior investigational product or procedure < 56 days preceding study entry (Baseline -Visit 2; Study Day 0).
8. Unwilling to discontinue use of nonprescription (OTC), nutritional or dietary supplements during the study period (as further defined by protocol).
9. Pregnant, lactating.
10. Any condition, personal or social situation that precludes or limits the ability of the participant to provide informed consent or comply with study requirements.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Dose arm 1	Drug: AFX-2; Dose level 1; Drug: AFX-2; Dose level 2; Drug: AFX-2; Dose level 3; Drug: AFX-2; Dose level 4; Drug: AFX-2; Dose level 5
Other: Dose arm 2	Drug: AFX-2; Dose level 1; Drug: AFX-2; Dose level 2; Drug: AFX-2; Dose level 3; Drug: AFX-2; Dose level 4; Drug: AFX-2; Dose level 5
Other: Dose arm 3	Drug: AFX-2; Dose level 1; Drug: AFX-2; Dose level 2; Drug: AFX-2; Dose level 3; Drug: AFX-2; Dose level 4; Drug: AFX-2; Dose level 5
Other: Dose arm 4	Drug: AFX-2; Dose level 1; Drug: AFX-2; Dose level 2; Drug: AFX-2; Dose level 3; Drug: AFX-2; Dose level 4; Drug: AFX-2; Dose level 5
Other: Dose arm 5	Drug: AFX-2; Dose level 1; Drug: AFX-2; Dose level 2; Drug: AFX-2; Dose level 3; Drug: AFX-2; Dose level 4; Drug: AFX-2; Dose level 5

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Afexa Life Sciences Inc
• Investigators: Principal Investigator: Leslie R Ellis, MD, Wake Forest University Health Sciences Center

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Anticipated): March 1, 2013
• Study Completion (Anticipated): May 1, 2013

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Estimate): January 25, 2012
• Last Update Submitted That Met QC Criteria: January 23, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: AFX-2-2010-1