Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia

Sponsor

OncoVista, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00709215

Collaborator

AAIPharma (Industry)

Enrollment

Locations

Duration (Months)

14.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a two-part, open-label, Phase I/II study in subjects with relapsed or refractory TdT-positive leukemia for which no standard therapies are expected to result in durable remission.

Condition or Disease	Intervention/Treatment	Phase
Refractory TdT-Positive Leukemia	Drug: Cordycepin plus Pentostatin	Phase 1/Phase 2

Detailed Description

In the first phase the Study Objectives are to:

Define the maximally tolerated dose (MTD) and recommended dose (RD) for administration of cordycepin as a 1-hour IV infusion, administered 1 hour following administration of an IV bolus of pentostatin, in subjects with refractory TdT-positive leukemia;
Determine plasma ADA levels prior to pentostatin infusion and at 60 and 120 minutes after administration of pentostatin;
Determine the single and multiple dose pharmacokinetics (PK) of cordycepin given 1 hour after a fixed dose of pentostatin;
Assess cordycepin pharmacodynamics by measurement of blast cell apoptosis from peripheral blood smears;
Measure and quantitate any clinical responses in refractory TdT-positive leukemia patients following cordycepin/pentostatin administration.

In the second phase, the Study Objectives are to assess the safety, PK, and clinical outcomes of cordycepin in combination with pentostatin, at the RD, in a 20 subject cohort

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia

Study Start Date :

Jun 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2010

Anticipated Study Completion Date :

Dec 1, 2010

Outcome Measures

Primary Outcome Measures

Establishment of the recommended dose (RD) of cordycepin, given one hour following a fixed dose of the ADA inhibitor pentostatin, in subjects with refractory TdT-positive leukemia [one year]

Secondary Outcome Measures

Determination of the single and multiple dose pharmacokinetics of cordycepin. Measurement and quantification any any clinical responses following administration of cordycepin/pentostatin at the recomme [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

TdT-positive leukemia (ALL, AML, or blastic CML) that has failed at least one standard treatment regimen and for which no standard therapies are expected to result in durable remission. Leukemia is minimally defined as at least 20% blast cells present in marrow or peripheral blood. TdT must be expressed in at least 20% of blast cells present and documented either immunologically or biochemically;
Age ≥18 years;
Must understand and voluntarily sign informed consent;
Adequate non-hematologic organ system function, defined by:
Creatinine ≤1.5 times the upper limit of normal (ULN) and/or creatinine clearance ≥60 mL/min
AST and/or ALT ≤2.5 times upper limit of normal (ULN)
Total bilirubin within institutional normal range
Normal EKG and LVEF >40%, measured by EKG and MUGA scan, radionuclide ventriculogram, or echocardiogram
Life expectancy >3 months;
Performance status (PS) >70% Karnofsky or ECOG ≤2;
Women of childbearing potential must have a negative serum pregnancy test within 7 days of starting study drug. A woman of child-bearing potential is a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months);
Male or female of child-bearing potential must agree to use adequate contraceptive methods

Exclusion Criteria:

Failure to meet inclusion criteria;
Uncontrolled active infection;
Extramedullary (CNS) disease;
Serious concomitant medical illness, such as active infection, uncontrolled congestive heart failure, or uncontrolled diabetes or other metabolic disorder, or psychiatric illness;
Pregnancy or lactation; females of child bearing potential must use adequate contraceptive methods;
Less than 3 weeks since prior chemotherapy, radiation therapy, or immunotherapy. However, hydroxyurea is permitted up to 24 hours before the study is initiated;
Less than 2 months following bone marrow or peripheral blood stem cell transplantation or treatment with donor lymphocyte infusion (DLI).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham & Women's Hospital	Boston	Massachusetts	United States	02115
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
3	Cancer Therapy Reasearch Center at UTHSCA	San Antonio	Texas	United States	78229

Sponsors and Collaborators

OncoVista, Inc.
AAIPharma

Investigators

Principal Investigator: Swaminathan Padmanabhan, MD, Cancer Therapy Research Center at UTHSCSA
Principal Investigator: Daneil J DeAngelo, MD, PhD., Dana Farber Cancr Institute