Trial Outcomes & Findings for 3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia (NCT NCT00381550)

NCT ID: NCT00381550

Last Updated: 2015-01-06

Results Overview

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.).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: Up to 4 years
• Results posted on: 2015-01-06

Participant Flow

Patient's presenting for treatment of a myeloproliferative disease were considered for participation.

Once patient consented to treatment, treatment began shortly there after.

Participant milestones

Measure	Triapine and Fludarabine Phosphate 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 Study STARTED	35
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Arm I n=35 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	18 Participants n=5 Participants
Age, Continuous	65 years STANDARD_DEVIATION 40 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 years

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.).

Outcome measures

Measure	Arm I n=35 Participants 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.
Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation	18 participants

PRIMARY outcome

Timeframe: Up to 4 years

Outcome measures

Measure	Arm I n=35 Participants 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.
Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0	35 participants

Adverse Events

Arm I

Serious events: 18 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I n=35 participants at risk 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.
Metabolism and nutrition disorders Hyperbilirubinemia	5.7% 2/35 • Number of events 2
Metabolism and nutrition disorders Tumor Lysis syndrome	8.6% 3/35 • Number of events 3
Infections and infestations Infections	20.0% 7/35 • Number of events 7
Investigations Kidney injury	17.1% 6/35 • Number of events 6

Other adverse events

Measure	Arm I n=35 participants at risk 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.
Metabolism and nutrition disorders Acidosis	28.6% 10/35 • Number of events 10
General disorders Allergic reaction	14.3% 5/35 • Number of events 5
General disorders Anaphylaxis	5.7% 2/35 • Number of events 2
Metabolism and nutrition disorders Elevated bilirubin	40.0% 14/35 • Number of events 14
Metabolism and nutrition disorders Elevated creatinine	22.9% 8/35 • Number of events 8
General disorders Fever	31.4% 11/35 • Number of events 11

Additional Information

Michael McDevitt, MD PhD

Sidney Kimmel Comprehensive Cancer Center

Phone: 410-955-9175

Email: mmcdev1@jhmi.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60