Trial of AVN-944 in Patients With Advanced Hematologic Malignancies

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Completed

CT.gov ID

NCT00273936

Collaborator

(none)

Enrollment

Locations

14.4

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and maximum tolerated dose, pharmacokinetics, and anti-neoplastic response of AVN-944 in patients with advanced hematologic malignancies.

Condition or Disease	Intervention/Treatment	Phase
Acute Leukemia Chronic Leukemia Multiple Myeloma Hodgkin's Lymphoma Non-Hodgkin's Lymphoma Waldenstrom's Macroglobulinemia	Drug: AVN-944 capsules for oral administration	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Official Title:

A Phase I Trial of AVN-944 in Patients With Advanced Hematologic Malignancies

Study Start Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed chronic myelogenous leukemia, acute myeloid leukemia, acute lymphocytic leukemia, multiple myeloma, Waldenstrom's macroglobulinemia, non-Hodgkin's lymphoma or Hodgkin's disease.
Patients must be refractory to, intolerant of, or decline to receive established therapy known to provide clinical benefit for their condition.
Age > 18 years
ECOG performance score of 0 or 1
Adequate renal function as evidenced by serum creatinine < 2.0 mg/dL
Adequate hepatic function as evidenced by:

Serum total bilirubin < 2.0 mg/dL (Patients with known Gilbert's syndrome may have total bilirubin values of up to 3 mg/dL.)
Alkaline phosphatase < 3X the upper limit of normal (ULN) for the reference lab (< 5X the ULN if considered related to underlying disease)
SGOT/SGPT < 3X the ULN for the reference lab (< 5X the ULN if considered related to underlying disease

Patients must be recovered from the clinically significant effects of any prior surgery, radiotherapy or other antineoplastic therapy.
Patients or their legal representatives must be able to read, understand and provide written informed consent to participate in the trial.
Women of childbearing potential as well as fertile men and their partners must agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method).

Exclusion Criteria:

Patients with an uncontrolled active infection
Prior treatment with an inosine-5-monophosphate dehydrogenase (IMPDH)-inhibitor
History of prior malignancy within the past 5 years except for curatively treated non-melanoma skin cancers, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate specific antigen (PSA) of < 1.0 mg/dL Patients with other curatively treated malignancies who have no evidence of metastatic disease may be entered after discussion with the Medical Monitor.
Patients with known hypersensitivity to any of the components of AVN-944
Patients who are receiving concurrent investigational therapy or who have received investigational therapy within 14 days of the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication). Clinically significant toxicities from this therapy must have resolved to < Grade 2.
Grade 2 peripheral neuropathy
Patients who are pregnant or lactating
Any other intercurrent medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign the informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
History of solid organ transplant
Known HIV or hepatitis B or C (active, previously treated or both)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center	Tucson	Arizona	United States	85715
2	Stanford Cancer Center	Stanford	California	United States	94305
3	George Washington University	Washington	District of Columbia	United States	20037
4	Ohio State University, James Cancer Hospital Comprehensive Cancer Center	Columbus	Ohio	United States	43210
5	Oregon Health and Science University	Portland	Oregon	United States	097239