**KEY MEASUREMENT UNITS FOR THE ENROLLMENT FORM (DOUBLE CHECK!)**
THESE VALUES ARE USED TO DETERMINE THE RANDOMIZATION STRATUM. AS PATIENTS ARE ENROLLED AND RANDOMIZED DIRECTLY FROM THE SITE, INCORRECT DATA ENTRY WILL RESULT IN THE INCORRECT STRATUM AND THE PATIENT BEING UNEVALUABLE.
FAQ:
Eligibility Questions
1.What is the enrollment window for the study?
Eligible patients MUST be enrolled prior to the START of Day 5 chemotherapy (ie prior to the morning steroid dose, which would mark the start of Day 5 chemotherapy). This does not include intrathecal therapy.
2.Are patients eligible if DXA cannot be performed?
Yes, these patients are still analyzable for the primary MRD endpoint and the other secondary biology endpoints. It is requested and would be preferable to have the DXA scan to be evaluable for the second primary endpoint (change in body fat), but it is not required to participate in the study.
Please note: the waist circumference at diagnosis and end of induction is required regardless of DXA (as an estimate of fat mass).
3.Are patients eligible if specimens cannot be collected for the laboratory studies?
Yes, patients are still eligible even if laboratory studies cannot be collected. For patients who cannot have diagnostic/baseline specimens enrolled, future laboratory specimens are still requested.
Radiology Questions
4.Should you obtain an End of Induction DXA if you cannot obtain the at diagnosis DXA?
Yes, DXA on Day 29 is still requested even without a baseline DXA at diagnosis.
Waist circumference at diagnosis and end of induction would still be required.
5.When is the latest a DXA scan can be completed? Can the DXA still be done on day 5 before the morning steroid?
The DXA scan should be completed as close to day 1 of chemotherapy as possible. The protocol timing was designed to give as much flexibility through the end of Day 4. However, a DXA could be performed on Day 5 prior to the AM steroid dose (which would mark the start of Day 5 chemotherapy) if necessary.
Laboratory Questions
6.What are the procedures for specimens that are obtained over the holiday weekend.
If it is possible for a local research laboratory to Ficoll and freeze viable mononuclear cells from the marrow/blood specimens, that would be greatly appreciated given the time sensitivity of the correlative biology studies. However, if Ficoll processing is not possible at the site, if the specimen would still arrive on a laboratory receipt day (as indicated in the laboratory manual) within 48 hours of collection, the sample may still be shipped. If Ficoll capabilities are not available, and timing is not feasible, the diagnostic specimen for viable cells would be omitted.
Frozen marrow/blood serum would still be requested as it is temporarily stored and batch shipped from the site.
7.How do you process BM within 6 hours of doing it at diagnosis when the child has not enrolled on the study?
This is for sites with an extra bone marrow/specimen mechanism, where specimens are collected, processed, and held prior to enrollment (or for sites that perform marrows after treatment and co-enrollment).
8.Our extra BM is stored in a fridge. How long could a BM be stored there before we spin it for plasma.
This is for metabolomics in the marrow, so would ideally be spun and frozen as close as possible to collection time and within the window specified in the lab manual. The database captures collection/frozen date and time to help us adjust analyses for longer gaps. There is no outside limit to the timing for marrow plasma collection/freezing.
9.In the protocol it says to draw the Peripheral Blood preferably before starting chemo. Is that before the day 5 morning steroid, or does it mean before Day 1 chemotherapy?
For patients with extra specimen processes, or for those consented before starting chemo (some places “tag-team” therapeutic + supportive care consents), it’s best to collect samples before starting Day 1 systemic chemotherapy. However, this is not mandatory.
From the protocol (footnote 5 in Section 6.1/Table 1) – “Bone marrow and peripheral blood for correlative biology at diagnosis should be collected as close to diagnosis as possible and prior to systemic chemotherapy (including cytoreductive therapy) is strongly preferred”
If the site sends the end of induction plasma sample fresh, will the CHLA/USC Lab be able to extract DNA from the sample?
Yes and alternatively sites can process the tubes themselves if they can ficoll either in a tube each or from same tube.
RD and PT Questions
10.By when do the RD and PT assessments and interventions at diagnosis need to be completed?
Both RD and PT visit is requested to occur as close to diagnosis/enrollment as possible. This is to both obtain as close to a “true” baseline assessment as is feasible, but also to start the intervention ASAP in those randomized to the intervention arm.
For the RD, the initial assessment (and the guidance/intervention for those randomized to the intervention arm), MUST be completed before start of chemotherapy on day 5 (AM steroid, see above re:DXA scans).
For the PT, the assessment (and the guidance/intervention for those randomized to the intervention arm) is requested to occur before day 5. The PT visit may occur through the end of Day 8 if necessary and MUST be completed by the end of Day 8. This extended timing was included in Amendment #1 due to common challenges from equipment needs/scheduling concerns with PT.
This timing is listed in the protocol (Footnote 7, section 6.1/Table 1).
11.For patients with obesity, should the RD use adjusted body weight or the actual body weight to calculate energy requirements? What about for patients who are borderline by BMI (BMI% 94.5-94.9) but not technically with obesity?
For patients who do not have obesity (i.e., BMI<95th percentile) use their actual body weight and height.
For patients with obesity (i.e., BMI >/= 95th percentile), use their actual height and adjusted body weight. Adjusted body weight is calculated as IBW + 0.25 (ABW – IBW) where IBW = weight (in kg) at the 50th percentile BMI for age. Please do not round up in these calculations.
For patients who are borderline obese, use the appropriate calculation for BMI at the time of assessment (e.g., BMI% 94.9 is without obesity = actual body weight; BMI% 95.1 is with obesity, use adjusted body weight).
12.As per Protocol Section 8.1, assessment data is requested for patients going off protocol therapy but staying on study. What specific data should be collected?
For these patients, data should be collected to mirror that for patients on the control arm.
General Procedure Questions
13.What is the timeframe to complete the PedsQL survey?
For PedsQL, it should be completed as close to diagnosis as possible. However, as there is not a specific window specified, it must be completed prior to Day 8 chemotherapy.
Billing Questions
14.How should Registered Dietitian (RD) and Physical Therapist (PT) visits be billed?
RD and PT visits are typically considered standard of care during cancer therapy. For sites where this is the case, standard of care visits, inclusive of the specific intervention requirements and assessments, may be used for the study. However, for sites where this is not the case, or for visits required prior to authorization being obtained, the study includes reimbursement for RD and PT time. This is included in the per-patient reimbursement and is not billed separately. The per-patient reimbursement may be spent however the site determines.
15.How should the DXA scan be billed?
DXA scans are research procedures. The per-patient reimbursement includes the typical cost of a DXA scan and is not billed separately. The per-patient reimbursement may be spent however the site determines.
Regulatory Questions
16.When should assent be obtained?
Database Clarifications
Liver Panel Form
17.When should the highest liver panel values be reported in the On Study Event and End of Induction Event?
For the On Study event: all highest liver panel values should be prior to either the initiation of chemotherapy or study consent, whichever occurs first.
For the End of Induction event: all highest liver panel values should be after the On-Study period but prior to the start of consolidation. These may include lab values from the morning of first day of consolidation PRIOR to start of systemic consolidation chemotherapy (intrathecal chemotherapy is allowed).
Toxicity Form
18.When is defined as “Baseline” for grading AST and ALT in accordance with CTCAE v.5?
Baseline should be considered the lowest value from presentation prior to Day 8 systemic chemotherapy (intrathecal chemotherapy allowed). This timing is incorporated due to frequent involvement of the liver from leukemia at presentation that improves with initiation of chemotherapy (i.e., transient, not innate liver dysfunction).
19.Do elevated AST, ALT and Bilirubin need to be reported as pre-existing conditions?
No.
20.Does pre-existing and known fatty liver disease need to be reported as a pre-existing condition?
Yes.