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

Purpose

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	Intervention	Phase
Refractory TdT-Positive Leukemia	Drug: Cordycepin plus Pentostatin	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Leukemia

Drug Information available for: Pentostatin

U.S. FDA Resources

Further study details as provided by OncoVista, Inc.:

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 [ Time Frame: one year ] [ Designated as safety issue: No ]

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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	44
Study Start Date:	June 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Cordycepin Plus Pentostatin on days 1, 2 and 3 of a 21 day cycle. Number of cycles until progression or unacceptable toxicity

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

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00709215

Contacts


Contact: Michael Moloney, MBA, BS	210.677.6000 ext 201	michael.moloney@oncovista.com

Locations


United States, Massachusetts
Brigham & Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Daniel J DeAngelo, MD, PhD. 617-632-2645 Daniel_Deangelo@dfci.harvard.edu
Principal Investigator: Daneil J DeAngelo, MD, PhD.
Sub-Investigator: Richard Stone, MD
Sub-Investigator: L. Andres Sirulnik, MD
Sub-Investigator: Martha Wadleigh, MD
Sub-Investigator: Gregory Abel, MD, MPH
Sub-Investigator: Susan L Buchanan, PA
Sub-Investigator: Adriana Penicaud, PA
Sub-Investigator: Ilene Galinsky, APRN
Sub-Investigator: Eyal Attar, MD
Sub-Investigator: Philip Amrein, MD
Sub-Investigator: Karen Kuhn Ballen, MD
United States, Texas
Cancer Therapy Reasearch Center at UTHSCA	Recruiting
San Antonio, Texas, United States, 78229
Contact: Swaminathan Padmanabhan, MD 210-450-5094 PadmanabhanS@uthscsa.edu
Sub-Investigator: Monica Mita, MD
Principal Investigator: Alain Mita, MD

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

More Information


Responsible Party:	Michael Moloney, Director - Program Management, OncoVista, Inc.
ClinicalTrials.gov Identifier:	NCT00709215 History of Changes
Other Study ID Numbers:	OV06-001
Study First Received:	June 30, 2008
Last Updated:	January 8, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by OncoVista, Inc.:


refractory TdT-positive leukemia ALL AML blastic CML

Additional relevant MeSH terms:


Leukemia Neoplasms by Histologic Type Neoplasms Cordycepin Pentostatin Antineoplastic Agents	Adenosine Deaminase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antifungal Agents Anti-Infective Agents

ClinicalTrials.gov processed this record on September 30, 2016