3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia

• ClinicalTrials.gov Identifier: NCT00381550
• Recruitment Status: Completed
• First Posted: September 28, 2006
• Results First Posted: May 21, 2014
• Last Update Posted: January 6, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia
• Interventions: Drug: fludarabine phosphate; Drug: triapine; Procedure: laboratory biomarker analysis
• Enrollment: 35

Participant Flow

Recruitment Details	Patient's presenting for treatment of a myeloproliferative disease were considered for participation.
Pre-assignment Details	Once patient consented to treatment, treatment began shortly there after.

Arm/Group Title	Triapine and Fludarabine Phosphate
Arm/Group Description	Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started	35
Completed	35
Not Completed	0

Baseline Characteristics

Arm/Group Title		Arm I
Arm/Group Description		Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants		35
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	17 48.6%
	>=65 years	18 51.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	35 participants
		65 (40)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	35 participants
	Female	18 51.4%
	Male	17 48.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	35 participants
		35

Outcome Measures

1. Primary Outcome

Title	Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation
Description	Bone marrow aspiration and biopsies were performed prior to treatment, during week 3 of the first cycle, at the time of hematologic recovery from all cycles of therapy (defined as neutrophil count >500/mm3 and platelets >20,000/mm3 independently of transfusion), or at any time that leukemia regrowth was suspected. The overall response rate was defined as complete remission, partial remission, or hematologic improvement, lasting for ≥30 days. Given the different subsets of diseases, standardized response criteria were used for CMML (the Myelodysplastic Syndrome International Working Group criteria),33 CMML transforming to acute myeloid leukemia (standard AML response criteria) , accelerated MPN (Giles et al.), and transformation of MPN to secondary AML (Mascarenhas et al.).
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description:	Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	35
Measure Type: Number; Unit of Measure: participants
	18

2. Primary Outcome

Title	Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0
Description	[Not Specified]
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description:	Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	35
Measure Type: Number; Unit of Measure: participants
	35

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm I
Arm/Group Description	Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Arm I
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	18/35 (51.43%)
Infections and infestations
Infections †	7/35 (20.00%)	7
Investigations
Kidney injury †	6/35 (17.14%)	6
Metabolism and nutrition disorders
Hyperbilirubinemia †	2/35 (5.71%)	2
Tumor Lysis syndrome †	3/35 (8.57%)	3
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I
	Affected / at Risk (%)	# Events
Total	35/35 (100.00%)
General disorders
Allergic reaction †	5/35 (14.29%)	5
Anaphylaxis †	2/35 (5.71%)	2
Fever †	11/35 (31.43%)	11
Metabolism and nutrition disorders
Acidosis †	10/35 (28.57%)	10
Elevated bilirubin †	14/35 (40.00%)	14
Elevated creatinine †	8/35 (22.86%)	8
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Michael McDevitt, MD PhD
• Organization: Sidney Kimmel Comprehensive Cancer Center
• Phone: 410-955-9175
• EMail: mmcdev1@jhmi.edu

Publications of Results:

Zeidner JF, Karp JE, Blackford AL, Smith BD, Gojo I, Gore SD, Levis MJ, Carraway HE, Greer JM, Ivy SP, Pratz KW, McDevitt MA. A phase II trial of sequential ribonucleotide reductase inhibition in aggressive myeloproliferative neoplasms. Haematologica. 2014 Apr;99(4):672-8. doi: 10.3324/haematol.2013.097246. Epub 2013 Dec 20.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00381550
• Other Study ID Numbers: NCI-2009-00209; NCI-2009-00209 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); J0638 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center ); 7704 ( Other Identifier: CTEP ); P30CA006973 ( U.S. NIH Grant/Contract ); U01CA070095 ( U.S. NIH Grant/Contract )
• First Submitted: September 26, 2006
• First Posted: September 28, 2006
• Results First Submitted: April 23, 2014
• Results First Posted: May 21, 2014
• Last Update Posted: January 6, 2015