Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy
Primary Purpose
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cholecalciferol
pharmacological study
cholecalciferol
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional supportive care trial for Adult Acute Megakaryoblastic Leukemia (M7)
Eligibility Criteria
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
Sites / Locations
- Roswell Park Cancer Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm I (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])
Arm II (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])
Arm Description
Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8.
Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8.
Outcomes
Primary Outcome Measures
Changes in 25(OH)-D3 levels after supplementation
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
Summarized using the mean (with corresponding 90% confidence intervals) and standard deviation.
Safety and toxicity parameters
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01521936
First Posted
January 26, 2012
Last Updated
June 18, 2015
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01521936
Brief Title
Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy
Official Title
Vitamin D3 Supplementation in Acute Myeloid Leukemia: Pharmacokinetic Study
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Why Stopped
Lack of funding
Study Start Date
December 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
June 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Untreated Adult Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])
Arm Type
Experimental
Arm Description
Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive lower-dose cholecalciferol PO beginning on day 8.
Arm Title
Arm II (25(OH)-D3 levels 20-31.9 ng/mL [insufficient levels])
Arm Type
Experimental
Arm Description
Patients receive a loading dose of cholecalciferol PO on day 1. Patients then receive higher-dose cholecalciferol PO beginning on day 8.
Intervention Type
Dietary Supplement
Intervention Name(s)
cholecalciferol
Other Intervention Name(s)
Calciol, Vitamin D3
Intervention Description
Given PO (lower dose)
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Dietary Supplement
Intervention Name(s)
cholecalciferol
Other Intervention Name(s)
Calciol, Vitamin D3
Intervention Description
Given PO (higher dose)
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Changes in 25(OH)-D3 levels after supplementation
Description
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.
Time Frame
From baseline to monthly for the first 3 months and then every 3 months
Title
Pharmacokinetic parameters
Description
Summarized using the mean (with corresponding 90% confidence intervals) and standard deviation.
Time Frame
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
Title
Safety and toxicity parameters
Description
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.
Time Frame
Daily for 21 days and monthly thereafter, up to 30 days after last dose of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meir Wetzler
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy
We'll reach out to this number within 24 hrs