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

Primary Purpose

Refractory TdT-Positive Leukemia

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cordycepin plus Pentostatin

About this trial

This is an interventional treatment trial for Refractory TdT-Positive Leukemia focused on measuring refractory TdT-positive leukemia, ALL, AML, blastic CML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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).

Sites / Locations

Brigham & Women's HospitalRecruiting
Dana Farber Cancer InstituteRecruiting
Cancer Therapy Reasearch Center at UTHSCARecruiting

Outcomes

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

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

Full Information

NCT ID

NCT00709215

First Posted

June 30, 2008

Last Updated

January 8, 2009

Sponsor

OncoVista, Inc.

Collaborators

AAIPharma

1. Study Identification

Unique Protocol Identification Number

NCT00709215

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2009

Overall Recruitment Status

Unknown status

Study Start Date

June 2008 (undefined)

Primary Completion Date

December 2010 (Anticipated)

Study Completion Date

December 2010 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

OncoVista, Inc.

Collaborators

AAIPharma

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Refractory TdT-Positive Leukemia

Keywords

refractory TdT-positive leukemia, ALL, AML, blastic CML

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Cordycepin plus Pentostatin

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Michael Moloney, MBA, BS

Phone

210.677.6000

Ext

201

michael.moloney@oncovista.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Swaminathan Padmanabhan, MD

Organizational Affiliation

Cancer Therapy Research Center at UTHSCSA

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Daneil J DeAngelo, MD, PhD.

Organizational Affiliation

Dana Farber Cancr Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham & Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Individual Site Status

Recruiting

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel J DeAngelo, MD, PhD.

Phone

617-632-2645

Daniel_Deangelo@dfci.harvard.edu

First Name & Middle Initial & Last Name & Degree

Daneil J DeAngelo, MD, PhD.

First Name & Middle Initial & Last Name & Degree

Richard Stone, MD

First Name & Middle Initial & Last Name & Degree

L. Andres Sirulnik, MD

First Name & Middle Initial & Last Name & Degree

Martha Wadleigh, MD

First Name & Middle Initial & Last Name & Degree

Gregory Abel, MD, MPH

First Name & Middle Initial & Last Name & Degree

Susan L Buchanan, PA

First Name & Middle Initial & Last Name & Degree

Adriana Penicaud, PA

First Name & Middle Initial & Last Name & Degree

Ilene Galinsky, APRN

First Name & Middle Initial & Last Name & Degree

Eyal Attar, MD

First Name & Middle Initial & Last Name & Degree

Philip Amrein, MD

First Name & Middle Initial & Last Name & Degree

Karen Kuhn Ballen, MD

Facility Name

Cancer Therapy Reasearch Center at UTHSCA

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Swaminathan Padmanabhan, MD

Phone

210-450-5094

PadmanabhanS@uthscsa.edu

First Name & Middle Initial & Last Name & Degree

Monica Mita, MD

First Name & Middle Initial & Last Name & Degree

Alain Mita, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

33225826

Citation

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.

Results Reference

derived

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

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