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

NCT01456182 | Withdrawn Phase 1

• 1 other identifier: AFX-2-2010-1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• 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

Study Arms (5)

Dose arm 1

OTHER

Drug: AFX-2

Dose arm 2

OTHER

Drug: AFX-2

Dose arm 3

OTHER

Drug: AFX-2

Dose arm 4

OTHER

Drug: AFX-2

Dose arm 5

OTHER

Drug: AFX-2

Interventions

AFX-2 DRUG

Dose level 1

Dose arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Afexa Life Sciences Inc: lead

Study Sites (3)

Saint Jospeh Mercy Health System

Ann Arbor, Michigan, 48106, United States

Location

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Cancer Center of the Carolinas

Greenville, South Carolina, 29615, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leslie R Ellis, MD

  Wake Forest University Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: May 1, 2013
• Last Updated: January 25, 2012

Record last verified: 2012-01

Locations

US (3)