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

Sponsor

Boston Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003005

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Cordycepin Drug: Deoxycoformycin	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 1997

Actual Primary Completion Date :

Mar 1, 2001

Actual Study Completion Date :

Mar 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Experimental: deoxycoformycin and cordycepin Dose escalation for deoxycoformycin and cordycepin	Drug: Cordycepin Dose escalation study using the following doses: 6mg/m2, 12 mg/m2, 24mg/m2, 48mg/m2 Drug: Deoxycoformycin Dose escalation using the Fibonacci dose escalation sequence starting dose 2mg/m2, escalating to 3mg/m3 intravenous Other Names: pentostatin, dCF

Arm

Intervention/Treatment

Experimental: deoxycoformycin and cordycepin

Dose escalation for deoxycoformycin and cordycepin

Drug: Cordycepin

Dose escalation study using the following doses: 6mg/m2, 12 mg/m2, 24mg/m2, 48mg/m2

Drug: Deoxycoformycin

Dose escalation using the Fibonacci dose escalation sequence starting dose 2mg/m2, escalating to 3mg/m3 intravenous

Other Names:

pentostatin, dCF

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose [28 days]
Dose limiting toxicities will be assessed within the first 28 days of study drug

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vincent T. Lombardi Cancer Research Center, Georgetown University	Washington	District of Columbia	United States	20007
2	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21287
3	New England Medical Center Hospital	Boston	Massachusetts	United States	02111
4	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
5	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
7	Boston Medical Center	Boston	Massachusetts	United States	02118
8	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
9	Washington University Barnard Cancer Center	Saint Louis	Missouri	United States	63110
10	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
11	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
12	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
13	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon	United States	97201-3098