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

NCT ID: NCT00709215

Last Updated: 2009-01-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-12-31

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.

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

Conditions

Refractory TdT-Positive Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Cordycepin plus Pentostatin

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

Intervention Type: DRUG

Eligibility 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

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AAIPharma

INDUSTRY

Sponsor Role: collaborator

OncoVista, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

OncoVista, Inc.

Principal Investigators

Swaminathan Padmanabhan, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Therapy Research Center at UTHSCSA

Daneil J DeAngelo, MD, PhD.

Role: PRINCIPAL_INVESTIGATOR

Dana Farber Cancr Institute

Locations

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Cancer Therapy Reasearch Center at UTHSCA

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michael Moloney, MBA, BS

Role: CONTACT

michael.moloney@oncovista.com

210.677.6000 ext. 201

Facility Contacts

Daniel J DeAngelo, MD, PhD.

Role: primary

Daniel_Deangelo@dfci.harvard.edu

617-632-2645

Swaminathan Padmanabhan, MD

Role: primary

PadmanabhanS@uthscsa.edu

210-450-5094

References

Verma AK. Cordycepin: a bioactive metabolite of Cordyceps militaris and polyadenylation inhibitor with therapeutic potential against COVID-19. J Biomol Struct Dyn. 2022 May;40(8):3745-3752. doi: 10.1080/07391102.2020.1850352. Epub 2020 Nov 23.

Reference Type: DERIVED

PMID: 33225826 (View on PubMed)

Other Identifiers

OV06-001

Identifier Type: -

Identifier Source: org_study_id