Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy

Phase 2

Terminated

• Conditions: Adult Acute Monoblastic Leukemia (M5a); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloblastic Leukemia With Maturation (M2)
• Interventions: Dietary Supplement: cholecalciferol; Other: pharmacological study; Other: laboratory biomarker analysis

• Registration Number: NCT01521936
• Lead Sponsor: Roswell Park Cancer Institute

Brief Summary

This partially randomized phase II trial studies the side effects and best way to give and best dose of cholecalciferol in treating patients with acute myeloid leukemia (AML) undergoing intensive induction chemotherapy. Cholecalciferol may help improve the outcome of patients with AML undergoing intensive chemotherapy

Detailed Description

PRIMARY OBJECTIVES: I. To assess patients with regards to changes in 25(OH)-D3 changes after supplementation. II. To develop a pharmacokinetic model to describe the time course of the relationship of vitamin D3 (cholecalciferol) supplementation that drives the levels of 25(OH)-D3 during the intensive induction chemotherapy. III. To determine the safety and toxicity of vitamin D3 supplementation in AML patients undergoing intensive induction chemotherapy. SECONDARY OBJECTIVES: I. To explore whether rapid (loading dose of vitamin D3) normalization of 25(OH)-D3 levels will have an effect on the progression free and overall survival. II. To explore whether a relationship exists between the pharmacokinetics of the 25-hydroxy-vitamin D3 and white blood cell count. OUTLINE: Patients with pretreatment 25(OH)-D3 levels 20-31.9 ng/mL (insufficient levels) are randomized to 1 of 2 treatment arms. ARM I: Patients receive a loading dose of cholecalciferol orally (PO) on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8. ARM II: Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8. Patients with pretreatment 25(OH)-D3 levels \< 20 ng/mL (deficient levels) receive a loading dose of cholecalciferol PO on days 1 and 8. Patients then receive lower-dose cholecalciferol PO beginning on day 15. For all patients, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-01-26
• Study First Submitted QC: 2012-01-26
• Study First Posted: 2012-01-31
• Primary Completion: 2013-03
• Status Verified: 2015-06
• Study Completion: 2015-06
• Last Update Submitted: 2015-06-18
• Last Update Posted: 2015-06-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Pathologic diagnosis of newly diagnosed AML (excluding acute promyelocytic leukemia [APL]) Patients undergoing intensive induction therapy (equivalent of 7+3, cytarabine, daunorubicin, etoposide [ADE] or high-dose cytarabine containing regimens) Subnormal 25(OH)-D3 levels (< 32 ng/mL) Serum calcium =< upper limit of normal Demonstrate the ability to swallow and retain oral medication Patients of child-bearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

Patients should not have a history of nephrocalcinosis Patients should not have received bisphosphonate treatment within 28 days before study entry Pregnant or nursing female patients Unwilling or unable to follow protocol requirements Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug Received an investigational agent within 30 days prior to enrollment Patients who cannot be discontinued from cimetidine, thiazide diuretics and/or heparin Patients who are on magnesium based antacids who cannot be offered an alternative regimen

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	pharmacological study	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8.
Arm II (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	pharmacological study	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8.
Arm II (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	laboratory biomarker analysis	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8.
Arm I (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	cholecalciferol	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8.
Arm II (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	cholecalciferol	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8.
Arm I (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])	laboratory biomarker analysis	Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8.

Primary Outcome Measures

Name	Time	Method
Changes in 25(OH)-D3 levels after supplementation	From baseline to monthly for the first 3 months and then every 3 months	The within-group pre- and post-supplementation levels will be summarized separately and the within-subject change will also be computed. To assess within-arm treatment effects the sign test will be used.
Pharmacokinetic parameters	30 minutes before administration, 30 minutes after administration, and 24 hours after administration on day 1; monthly for the first 3 months; and then every 3 months	Summarized using the mean (with corresponding 90% confidence intervals) and standard deviation.
Safety and toxicity parameters	Daily for 21 days and monthly thereafter, up to 30 days after last dose of study drug	Rates corresponding to toxicity endpoints will be estimated using simple relative frequencies. The corresponding 90% confidence intervals for the estimated probabilities will be computed using the method proposed in Clopper and Pearson. Comparison between groups will be done in an exploratory fashion using appropriate two-sample tests. A nominal significance level of 0.10 will be used in all testing.

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States