Oral Clofarabine for Acute Myeloid Leukemia

NCT00727766 | Completed Phase 1 DMC

• 1 other identifier: 08-0853 / 201108049
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I study designed to test the safety of oral clofarabine when given as consolidation therapy to older patients with AML in remission.

Conditions

Leukemia, Myeloid, Acute

Keywords

Clofarabine; Clolar; AML; Consolidation

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) and dose limiting toxicity (DLT)

  DLT - 1st cycle (28 days), MTD - completion of 1st cycle by all patients in all cohorts

Secondary Outcomes (3)

• Adverse events by grade and attribution

  Start of treatment through 30 days post-last dose

• Disease-free survival

  Every 6 months for 3 years

• Overall survival

  Every 6 months for 3 years

Study Arms (6)

Cohort 1

EXPERIMENTAL

Clofarabine 1 mg for 14 days followed by 14 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Cohort 2

EXPERIMENTAL

Clofarabine 2 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Cohort 3

EXPERIMENTAL

Clofarabine 3 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Cohort 4

EXPERIMENTAL

Clofarabine 4 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Cohort 5

EXPERIMENTAL

Clofarabine 5 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Cohort 6

EXPERIMENTAL

Clofarabine 6 mg for 21 days followed by 7 days of rest. Each cycle is 28 days long.

Drug: Clofarabine

Interventions

Clofarabine DRUG

Also known as: Clolar

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Acute Myeloid Leukemia according to WHO criteria
• Age ≥ 60 years at enrollment
• Patients must be in complete remission by bone marrow examination, within 30 days of enrollment, following treatment with a cytotoxic induction chemotherapy regimen (such as 7+3)
• Complete remission must be confirmed by bone marrow biopsy
• If one cycle of consolidation was administered, then patient may be within 60 days of the confirmation of complete remission by bone marrow biopsy
• Minimum platelet count of 100,000
• Patients may have received "low-intensity" therapy (i.e. decitabine, lenalidomide, etc) prior to traditional induction chemotherapy.
• Patients may have received 1 cycle of cytarabine-based consolidation therapy.
• Patients must have an ECOG performance status of 0-2 at the beginning of consolidation therapy.
• Have adequate renal and hepatic functions as indicated by the following laboratory values:
• Serum creatinine ≤ 1.0 mg/dL; if serum creatinine \>1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be \>60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
• Serum total bilirubin ≤ 1.5 mg/dL × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia secondary Gilbert's syndrome
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN
• Alkaline phosphatase ≤ 2.5 × ULN
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide signed valid written informed consent or when appropriate, have an appointed legally authorized representative who is capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide signed valid written informed consent for the benefit of the patient.

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• The diagnosis of AML-M3 (acute promyelocytic leukemia) characterized by translocations involving the retinoic acid receptor-alpha (RAR-alpha) gene.
• Use of investigational agents within 2 weeks or any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Jacoby MA, Martin MG, Uy GL, Westervelt P, Dipersio JF, Cashen A, Stockerl-Goldstein K, Vij R, Luo J, Reineck T, Bernabe N, Abboud CN. Phase I study of oral clofarabine consolidation in adults aged 60 and older with acute myeloid leukemia. Am J Hematol. 2014 May;89(5):487-92. doi: 10.1002/ajh.23663. Epub 2014 Mar 3.

  PMID: 24415560 DERIVED

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Camille N. Abboud, M.D.

  Washington Univerisity

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2008
• First Posted: August 4, 2008
• Study Start: January 1, 2009
• Primary Completion: September 1, 2012
• Study Completion: November 1, 2014
• Last Updated: November 11, 2014

Record last verified: 2014-11

Locations

US (1)