Biomarkers in Predicting Treatment Response to Sirolimus and Chemotherapy in Patients With High-Risk Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT02583893|
Recruitment Status : Recruiting
First Posted : October 22, 2015
Last Update Posted : December 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia||Drug: Sirolimus Drug: Mitoxantrone Drug: Etoposide Drug: Cytarabine||Phase 2|
I. To test the association between biochemical response and clinical response.
I. To estimate complete response rate of sirolimus MEC in patients with high risk AML.
II. To estimate progression free survival in this patient population. III. To collect further information on the safety, tolerability, and efficacy of sirolimus in combination with MEC in patients with relapsed or refractory myeloid malignancies.
Patients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus orally (PO) on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride intravenously (IV) over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8.
After completion of study treatment, patients are followed up every 3 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||A Biomarker Validation Study to Establish Whether Serial Flow Cytometric Measurements Predict Clinical Response to Sirolimus and MEC (Mitoxantrone Etoposide Cytarabine) Treatment in Patients With High-Risk Acute Myelogenous Leukemia|
|Actual Study Start Date :||October 7, 2015|
|Estimated Primary Completion Date :||October 8, 2021|
|Estimated Study Completion Date :||January 2022|
Experimental: Sirolimus, MEC chemotherapy
Patients undergo collection of bone marrow samples prior to sirolimus dosing on day 4 and within 1 week and no later than day 45 of hematologic recovery. Patients receive sirolimus PO on days 2-9 (loading dose on day 1 only), and standard MEC chemotherapy comprising mitoxantrone hydrochloride IV over 15 minutes, etoposide IV over 1 hour, and cytarabine IV over 1 hour every 24 hours on day 4-8.
Other Name: Rapamycin
- Biochemical response [ Time Frame: Baseline to day 4 ]Defined by change in phosphorylated ribosomal protein S6 (pS6) positive blasts, measured as the % reduction in pS6 positive blasts from baseline to day 4. Biochemical response will be described by mean, median, standard deviation, range and coefficient of variation. The association between biochemical response and clinical response will be tested by Fisher's exact test.
- Clinical response [ Time Frame: Day 45 ]Based on hematologic recovery/day 45 marrow assessed according to International Working Group (IWG) criteria. The association between biochemical response and clinical response will be tested by Fisher's exact test.
- Incidence of adverse events [ Time Frame: Up to day 45 ]Recorded and graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Worse toxicity grades observed during treatment will be described. Toxicities will be graded and tabled.
- Overall response rate (ORR) (complete response [CR], CR with incomplete platelet recovery [CRp], or partial response) [ Time Frame: Day 45 ]Fraction of patients who achieve CR, CRp, or PR will be assessed. ORR and 95% exact confidence interval will be computed for all patients and for sensitive and resistant subgroups.
- Relapse free survival (RFS) [ Time Frame: Time from study entry to first documented progression, death, or last contact, assessed up to 2 years ]RFS will be estimated by the Kaplan-Meier method. A landmark analysis of RFS by clinical response (CR+CRp, CRi, PR or no response [NR]) will be computed from day 45 marrow assessment. Median values and 95% confidence intervals will be calculated.
- Overall survival (OS) [ Time Frame: Time from study entry to death or last contact, assessed up to 2 years ]OS will be estimated by the Kaplan-Meier method. A landmark analysis of RFS by clinical response (CR+CRp, CRi, PR or NR) will be computed from day 45 marrow assessment. Median values and 95% confidence intervals will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02583893
|Contact: Neil Palmisiano, MD||215-955-8874|
|Contact: Clinical Trials Office||215-955-1661|
|United States, Pennsylvania|
|Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Neil Palmisiano, MD 215-955-8874|
|Contact: Clinical Trials Office 215-955-1661|
|Principal Investigator: Neil Palmisiano, MD|
|Sub-Investigator: Neal Flomenberg, MD|
|Sub-Investigator: Joanne Filicko-O'Hara, MD|
|Sub-Investigator: Manish Sharma, MD|
|Sub-Investigator: John Wagner, MD|
|Sub-Investigator: Matthew Carabasi, MD|
|Sub-Investigator: S. Onder Alpdogan, MD|
|Sub-Investigator: Mark Weiss, MD|
|Sub-Investigator: Ubaldo Martinez Outschoorn, MD|
|Sub-Investigator: Thomas Klumpp, MD|
|Sub-Investigator: Michael Ramirez, MD|
|Sub-Investigator: Sameh Gaballa, MD|
|Principal Investigator:||Neil Palmisiano, MD||Thomas Jefferson University|