8-Chloroadenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia Clinical Trial

Official title: A Phase I/II Trial of 8-Chloro-Adenosine in Relapsed or Refractory Acute Myeloid Leukemia

Status Completed

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of 8-chloroadenosine and to see how well it works in treating patients with acute myeloid leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as 8-chloroadenosine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase II dose, RP2D) of 8-chloro-adenosine, when given as a single agent, in patients with relapsed or refractory acute myeloid leukemia. (Phase I) II. To assess tolerability and safety of 8-chloro-adenosine at each dose level by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (Phase I) III. To estimate the response rate and to evaluate the antitumor activity of 8-chloro-adenosine, when given as a single agent, as assessed by complete remission rate (complete remission [CR] + complete remission with incomplete blood count recovery [CRi]). (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate for disease response to 8-chloro-adenosine in refractory/relapsed acute myeloid leukemia (AML) on each dose level tested. (Phase I) II. To obtain estimates of remission duration and survival probabilities (overall and event-free). (Phase II) III. To obtain an estimate of the overall response rate (CR + CRi + partial response [PR]). (Phase II) IV. To summarize and evaluate toxicities by type, frequency, severity, attribution, time course and duration. (Phase II)

CLINICAL PHARMACOLOGY OBJECTIVES:

I. To describe the plasma, urinary and cellular pharmacokinetics of 8-chloro-adenosine and metabolites.

II. To determine the impact of 8-chloro-adenosine on cellular adenosine triphosphate (ATP) pool in AML blasts.

III. To assess the impact of 8-chloro-adenosine therapy on select short-lived messenger (m) ribonucleic acids (RNAs) and corresponding proteins in circulating AML blasts.

IV. To correlate clinical responses and toxicity with plasma/urine 8-chloro-adenosine level (pharmacokinetic [PK]), cellular 8-chloro-ATP (PK) and cellular ATP pool.

EXPLORATORY EX-VIVO MOLECULAR OBJECTIVES:

I. To determine the cytotoxicity of 8-chloro-adenosine toward leukemic progenitor cells in vitro.

II. To generate a preliminary pre-treatment RNA/micro RNA (miRNA) signature in leukemic progenitor cells, and explore its possible association with in vitro cytotoxicity to 8-chloro-adenosine.

III. To explore the possible association between the preliminary RNA/miRNA signature and clinical response to 8-chloro-adenosine.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive 8-chloro-adenosine intravenously (IV) over 4 hours on days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 2 years. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT02509546
• Study type: Interventional
• Source: City of Hope Medical Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2, 2015
• Completion date: March 16, 2021