Clinical trial · Interventional

3-AP Followed By Fludarabine In Treating Patients With Relapsed or Refractory Acute or Chronic Leukemia or High-Risk Myelodysplastic Syndrome

A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias

NCT00077558CI-TRIAL-00003250completedPhase 1ClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.

Conditions

Conditions (3)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90
Myelodysplastic/Myeloproliferative Diseases	Myelodysplastic/Myeloproliferative Neoplasm	ALIAS	0.90
Myelodysplastic Syndromes	Myelodysplastic Syndrome	ALIAS	0.90

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
fludarabine phosphate	Drug	Fludarabine	ALIAS
triapine	Drug	—	UNRESOLVED

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of 1 of the following:

  * High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia

    * International Prognostic Scoring System (IPSS) score at least 1.5 based on the following:

      * More than 10% marrow blasts
      * Cytopenias in at least 2 lineages
      * Adverse cytogenetics
  * Acute myeloid leukemia (AML)

    * All subtypes, including MDS/AML and treatment-related (secondary) AML
  * Acute lymphoblastic leukemia
  * Acute progranulocytic leukemia

    * Ineligible for arsenic therapy
  * Chronic myelogenous leukemia

    * Accelerated phase or blastic crisis
  * Chronic lymphocytic leukemia
  * Prolymphocytic leukemia
* Received or ineligible for established curative regimens, including stem cell transplantation
* Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* No history of hemolytic anemia grade 2 or greater
* No known glucose-6-phosphate dehydrogenase (G6PD) deficiency

  * G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)

Hepatic

* SGOT and SGPT no greater than 2.5 times normal
* Bilirubin no greater than 2 mg/dL
* No chronic hepatitis

Renal

* Creatinine normal OR
* Creatinine clearance at least 60 mL/min

Cardiovascular

* No active heart disease
* No myocardial infarction within the past 3 months
* No severe coronary artery disease
* No arrhythmias (other than atrial flutter or fibrillation) requiring medication
* No uncontrolled congestive heart failure

Pulmonary

* No dyspnea at rest or with minimal exertion
* No severe pulmonary disease requiring supplemental oxygen

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No neuropathy grade 2 or greater
* No active uncontrolled infection

  * Infections under active treatment and controlled by antibiotics are allowed
* No other life-threatening illness
* No psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim \[G-CSF\], sargramostim \[GM-CSF\], interleukin-3, and interleukin-11)
* No concurrent immunotherapy

Chemotherapy

* Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects)
* At least 72 hours since prior hydroxyurea
* At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas)
* No more than 12 prior courses of fludarabine
* No more than 3 prior cytotoxic chemotherapy regimens
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* At least 2 weeks since prior radiotherapy
* No concurrent radiotherapy

Surgery

* Not specified

Other

* At least 1 week since prior non-myelosuppressive treatment
* No more than 4 prior induction regimens
* No other concurrent therapy

References

Publications (1)

RESULTKarp JE, Giles FJ, Gojo I, Morris L, Greer J, Johnson B, Thein M, Sznol M, Low J. A phase I study of the novel ribonucleotide reductase inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) in combination with the nucleoside analog fludarabine for patients with refractory acute leukemias and aggressive myeloproliferative disorders. Leuk Res. 2008 Jan;32(1):71-7. doi: 10.1016/j.leukres.2007.05.003. Epub 2007 Jul 20. PMID 17640728

Registry

Dates and enrollment

Start: Jan 1, 2004
Primary completion: —
Completion: —
First posted: Feb 12, 2004
Last update posted: Mar 10, 2010
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins OTHER
Collaborators: National Cancer Institute (NCI)
Keywords: accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, refractory chronic lymphocytic leukemia, recurrent adult acute lymphoblastic leukemia, prolymphocytic leukemia, refractory anemia with excess blasts, chronic myelomonocytic leukemia, recurrent adult acute myeloid leukemia, secondary acute myeloid leukemia, adult acute minimally differentiated myeloid leukemia (M0), adult acute monocytic leukemia (M5b), adult acute erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4), adult acute monoblastic leukemia (M5a), adult acute promyelocytic leukemia (M3), adult acute eosinophilic leukemia, adult acute basophilic leukemia, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)

Data updated 22 days agoSource updated Mar 10, 2010

Brief summary (as posted)

Conditions (3)

Interventions (2)

Eligibility (as posted)

Publications (1)

Locations by country (4)