Epigenetic Reprogramming in Relapse AML

Conditions

• Leukemia, Acute Myeloid

Eligibility Criteria

Sex

ALL

Age

1 Year - 25 Years

Healthy Volunteers

Not accepted

Interventions

• Decitabine — DRUG
  Dosing per protocol starting at hour 0 IV infusion over 1 hour on Days 1-5
• Vorinostat — DRUG
  180 mg per meter squared per day for those under age 18, 300mg BID for those age 18 and older. Given after the decitabine infusion by mouth on Days 1-5
• Fludarabine — DRUG
  30 mg per meter squared per day starting at hour 0 given immediately after G-CSF by IV infusion over 30 minutes on days 6-10
• Cytarabine — DRUG
  2000 mg per meter squared per day starting at hour 4 by IV over 3 hours on days 6-10
• Filgrastim — DRUG
  5 μ/kg/dose starting at hour 0 immediately before fludarabine by IV or SQ on days 5-12
• Cytarabine — DRUG
  Patient Age (years) IT Cytarabine Dose \> 1 30 mg * 2 and \< 3 50 mg * 3 and ≤ 18 70 mg \> 18 100 mg given IT on day 0 or -1
• Sorafenib — DRUG
  150 mg/m2/dose twice daily by mouth on days 11-28

Study Details

Successful treatment for children and young adults with relapsed acute myeloid leukemia (AML) continues to be a significant challenge. Despite relative improvements in survival for patients with newly diagnosed AML, an estimated 40-60% will relapse with the majority eventually dying of their relapsed disease. Attaining a subsequent remission in patients who relapse is the initial critical step toward achieving a potential cure. As chemotherapy resistance is one of the primary drivers of poor treatment response and subsequent relapse in AML, identifying methods to reverse this resistance are desperately needed. This clinical trial is aimed at improving the remission re-Induction rates for children and adults with relapsed or refractory AML through epigenetic modifying agents that have the ability to reverse chemotherapy resistance. Decitabine, a DNA methyltransferase inhibitor (DNMTi) and Vorinostat, a histone deacetylase inhibitor (HDACi), are two epigenetic modifying drugs that act on the methylation of proximal promoter regions of genes and on proteins involved in the wrapping of DNA around histones, respectively. Both processes play a critical role in regulating gene expression, and frequently these genes are involved in chemotherapy resistance. These agents are FDA-approved for treatment in adult hematologic malignancies, making this an opportune time to begin testing these novel therapies in pediatric leukemia trials. This study will investigate chemotherapy priming of relapsed/refractory AML using Decitabine and Vorinostat given for 5 days prior to standard re-Induction with Fludarabine, Cytarabine and G-CSF for children and adults.

Key Dates

Start date

Feb 21, 2015

Status verified

Jan 2019

Primary completion

Jun 21, 2017

Completion

Jun 21, 2017

Study Design

Enrollment

3 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Treatment Plan - 2 treatment courses
  Drug Method Used to Give Drug Days Cytarabine IT 0 or -1 Decitabine IV over 1 hour 1-5 Vorinostat PO 1-5 Fludarabine IV over 30 minutes 6-10 Cytarabine IV over 3 hours 6-10 Filgrastim (G-CSF) IV or SQ 5-12 Sorafenib PO 11-28

Primary Outcome Measure

Achievement of Complete Remission by Bone Marrow Criteria [ Time Frame: 60 days ]

Locations (2)

Find similar trials in Minneapolis, MN

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