Chemotherapy With Cordycepin Plus Pentostatin in Treating Patients With Refractory Acute Lymphocytic or Chronic Myelogenous Leukemia

Leukemia Clinical Trial

Official title:

A Phase I Study of Cordycepin (NSC 63984) Plus 2'-Deoxycoformycin (NSC 218321) in Patients With Refractory TdT-Positive Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003005
• Other study ID #: CDR0000065572
• Secondary ID: BUMC-4266NCI-T96
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: June 12, 2012
• Start date: December 1997
• Est. completion date: March 2001

Study information

• Verified date: June 2000
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of chemotherapy consisting of cordycepin plus pentostatin in treating patients with refractory acute lymphocytic or chronic myelogenous leukemia.

Description:

OBJECTIVES: I. Evaluate the safety, maximum tolerated dose, adverse effects, and toxicities of cordycepin, given 1 hour following a fixed dose of the adenosine deaminase inhibitor pentostatin, in patients with refractory TdT positive leukemia. II. Determine the single and multiple dose pharmacokinetics of cordycepin given 1 hour following a fixed dose of pentostatin. III. Characterize selected whole blood and blast cell metabolic parameters serially in relation to cordycepin/pentostatin administration. IV. Measure and quantify any clinical responses in refractory TdT positive leukemia patients following cordycepin/pentostatin administration.

OUTLINE: This is a dose escalation study. Each treatment course is 28 days in length. On days 1-3 pentostatin is administered over 5 minutes by IV bolus and followed 1 hour later by a 1 hour infusion of cordycepin IV. An escalating dose of pentostatin is given with a fixed dose of cordycepin until the desired level of adenosine deaminase inhibition is observed. After this is determined, a dose escalation schedule for cordycepin is initiated to determine the maximum tolerated dose (MTD) when given in combination with pentostatin. The MTD is determined by the number of patients who exhibit dose limiting toxicity and the severity of the toxicity.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: March 2001
• Est. primary completion date: March 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS: TdT positive acute lymphocytic leukemia or blastic chronic myelogenous leukemia Failed at least one standard treatment

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky greater than 70% Life expectancy: At least 3 months Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL Transaminases no greater than 2.5 times normal Renal: Creatinine no greater than 1.5 mg/dL Creatinine clearance greater than 60 mL/min Cardiovascular: Ejection fraction greater than 40% Other: Not pregnant or nursing No serious concurrent illness

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 3 weeks since chemotherapy No concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since radiation therapy Surgery: Not specified

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Cordycepin
Dose escalation study using the following doses: 6mg/m2, 12 mg/m2, 24mg/m2, 48mg/m2
• Deoxycoformycin
Dose escalation using the Fibonacci dose escalation sequence starting dose 2mg/m2, escalating to 3mg/m3 intravenous

Locations

Country	Name	City	State
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	New England Medical Center Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon
United States	Washington University Barnard Cancer Center	Saint Louis	Missouri
United States	Vincent T. Lombardi Cancer Research Center, Georgetown University	Washington	District of Columbia
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose	Dose limiting toxicities will be assessed within the first 28 days of study drug	28 days	Yes