Trial Outcomes & Findings for Nutrition and Body Composition in Acute Lymphoblastic Leukemia (NCT NCT01317940)

Results Overview

Change in Vitamin D levels from baseline to study end (Group A: Consolidation through end of Delayed Intensification)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

76 participants

Primary outcome timeframe

+6 months

Results posted on

2020-07-08

Participant Flow

Group A: 2 participants enrolled but did not reach time of randomization (1 induction death, 1 severe toxicity/change in treatment plan) Group B: 2 subjects enrolled but did not reach time of randomization or undergo any study procedures (2 lost to follow-up)

Participant milestones

Participant milestones
Measure	On-Therapy Intervention (Group A) Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) Subjects randomized following Induction to receive standard of care with education alone OR subjects ineligible for open-label randomization and followed as "natural history" cohort.	On-Therapy "Natural History" (Group A) Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction	Survivorship Intervention (Group B) Subjects randomized to receive education plus directly-observed therapy with open-label Vitamin D and chewable calcium	Survivorship Standard of Care (Group B) Survivors randomized to receive standard of care with education alone OR subjects ineligible for open-label Vitamin D+ Calcium randomization and continued with follow-up only.	Siblings of Survivors (Group C) Healthy siblings of survivors of pediatric acute lymphoblastic leukemia (ALL) for one-time assessment
Overall Study STARTED	19	10	20	6	13	4
Overall Study COMPLETED	18	10	15	5	12	4
Overall Study NOT COMPLETED	1	0	5	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	On-Therapy Intervention (Group A) Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On-Therapy "Natural History" (Group A) Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction	Survivorship Intervention (Group B) Subjects randomized to receive education plus directly-observed therapy with open-label Vitamin D and chewable calcium	Survivorship Standard of Care (Group B) Survivors randomized to receive standard of care with education alone OR subjects ineligible for open-label Vitamin D+ Calcium randomization and continued with follow-up only.
Overall Study Death	1	1	0	0
Overall Study Lost to Follow-up	0	1	1	1
Overall Study Change in therapy plan	0	3	0	0

Baseline Characteristics

Nutrition and Body Composition in Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	On Therapy Intervention (Group A) n=19 Participants Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) n=10 Participants Subjects randomized following Induction to receive standard of care with education alone	On Therapy "Natural History" (Group A) n=20 Participants Subjects surviving to end of Induction but ineligible for randomization for any reason	Survivorship Intervention (Group B) n=6 Participants Survivors to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6 months)	Survivorship Standard of Care (Group B) n=13 Participants Survivors either randomized to received standard of care with education alone OR vitamin D sufficient and continued for follow-up only.	Siblings (Group C) n=4 Participants Healthy siblings of subjects in Group A	Total n=72 Participants Total of all reporting groups
Age, Continuous	15 years n=5 Participants	15 years n=7 Participants	14 years n=5 Participants	19 years n=4 Participants	18 years n=21 Participants	15 years n=10 Participants	15 years n=115 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	4 Participants n=10 Participants	29 Participants n=115 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	3 Participants n=4 Participants	10 Participants n=21 Participants	0 Participants n=10 Participants	43 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants	5 Participants n=4 Participants	5 Participants n=21 Participants	3 Participants n=10 Participants	54 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	12 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants
Region of Enrollment United States	19 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants	6 participants n=4 Participants	13 participants n=21 Participants	4 participants n=10 Participants	72 participants n=115 Participants

PRIMARY outcome

Timeframe: +6 months

Population: Includes subjects in each group evaluable for vitamin D endpoint. Calculation of change = Vitamin D level at study end (end of DI, \~+6 months)/Vitamin D level at baseline (start of consolidation).

Change in Vitamin D levels from baseline to study end (Group A: Consolidation through end of Delayed Intensification)

Outcome measures

Outcome measures
Measure	On-Therapy Intervention (Group A) n=18 Participants Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) n=10 Participants Subjects randomized following Induction to receive standard of care with education alone OR subjects ineligible for open-label randomization and followed as "natural history" cohort.	On-Therapy "Natural History" (Group A) n=15 Participants Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction
Change in Serum Vitamin D Level (Group A) Change in serum Vitamin 25(OH)D level	5.5 ng/ml Standard Error 1.7	-0.30 ng/ml Standard Error 2.2	1.0 ng/ml Standard Error 2.6
Change in Serum Vitamin D Level (Group A) Post-intervention serum Vitamin 25(OH)D level	26.5 ng/ml Standard Error 12.4	19.0 ng/ml Standard Error 7.4	23.3 ng/ml Standard Error 2.8

SECONDARY outcome

Timeframe: +6 months

Population: Subjects enrolled following the change to the open-label randomization were imaged for cortical bone density at the femur, subjects enrolled prior to this in the Natural History group were imaged at the tibia. The change was made for later subjects due to technical reasons to provide a better estimate of cortical density.

Bone mineral density (vBMD) at end of study period (Group A: end of Delayed Intensification)

Outcome measures

Outcome measures
Measure	On-Therapy Intervention (Group A) n=17 Participants Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) n=10 Participants Subjects randomized following Induction to receive standard of care with education alone OR subjects ineligible for open-label randomization and followed as "natural history" cohort.	On-Therapy "Natural History" (Group A) n=14 Participants Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction
Bone Mineral Density by Quantitative Computed Tomography (QCT) at Study End (Group A) Cortical BMD	2093.1 cm3 Standard Deviation 62.5	2090.9 cm3 Standard Deviation 26.7	927.5 cm3 Standard Deviation 65.3
Bone Mineral Density by Quantitative Computed Tomography (QCT) at Study End (Group A) Cancellous BMD	203.8 cm3 Standard Deviation 77.1	201.4 cm3 Standard Deviation 66.4	159.1 cm3 Standard Deviation 54.9

SECONDARY outcome

Timeframe: +6 months

Population: Change in Vitamin D = Vitamin D at +6months/Vitamin D at baseline

Change in serum vitamin D level was assessed in survivors at baseline and after 6 months of supplementation

Outcome measures

Outcome measures
Measure	On-Therapy Intervention (Group A) n=5 Participants Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) n=12 Participants Subjects randomized following Induction to receive standard of care with education alone OR subjects ineligible for open-label randomization and followed as "natural history" cohort.	On-Therapy "Natural History" (Group A) Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction
Change in Vitamin D Level (Group B) Change in serum Vitamin 25(OH)D level	1.0 ng/ml Standard Error 2.2	-1.0 ng/ml Standard Error 2.1	—
Change in Vitamin D Level (Group B) Post-intervention serum Vitamin 25(OH)D level	26.0 ng/ml Standard Error 2.0	29.0 ng/ml Standard Error 2.9	—

SECONDARY outcome

Timeframe: +6 months

Bone mineral density (vBMD) at end of study period (Group B: after 6 months)

Outcome measures

Outcome measures
Measure	On-Therapy Intervention (Group A) n=5 Participants Subjects randomized following Induction to receive education plus: Vitamin D and Calcium Citrate: Vitamin D (10,000 int.units/ml) 100,000 int. units (10ml) by mouth once every two months x 3 times (total treatment period approximately 6-7 months) Calcium Carbonate (1,000 mg/tab = 400 mg elemental calcium/tab) 2,000 mg (2 chewable tabs) by mouth every day through study period (total treatment period approximately 6-7 months)P	On Therapy Standard of Care (Group A) n=7 Participants Subjects randomized following Induction to receive standard of care with education alone OR subjects ineligible for open-label randomization and followed as "natural history" cohort.	On-Therapy "Natural History" (Group A) Patients enrolled prior to open-label randomization and those not eligible for randomization at end of induction
Bone Mineral Density by QCT in Survivors at Study End (Group B) Cancellous bone mineral density	243.6 cm3 Standard Deviation 28.7	269.3 cm3 Standard Deviation 80.0	—
Bone Mineral Density by QCT in Survivors at Study End (Group B) Cortical bone mineral density	2087.4 cm3 Standard Deviation 39.3	2049.3 cm3 Standard Deviation 73.0	—

SECONDARY outcome

Timeframe: 1 timepoint

Population: Group C: Only four siblings enrolled and arm closed early due to poor accrual. Specimens from this group were not analyzed so no results are available. Group A: 39 subjects enrolled at diagnosis had Vitamin D testing performed at diagnosis and had results available.

Insufficiency defined as 25(OH)D \< 30 ng/ml