Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma

Prior treatment

• Treatment with any medication in the past 3 months with the intention to lose weight (semaglutide, tirzepatide, liraglutide, phentermine, topiramate, naltrexone hydrochloride (HCl)/bupropion HCl, lorcaserin).
• Participant has contraindication to phentermine/topiramate ER by package insert (glaucoma or increased intraocular pressure, untreated hyperthyroidism, recent monoamine oxidase inhibitor (MAOI) inhibitor use).
• Prior bariatric surgery.
• Participant has a history of bipolar disorder, psychosis, prior suicide attempt or current moderate severity depression (PHQ-9 of 10 or more), report of suicidal ideation in the past 3 months, or self-injurious behavior in the past 3 months.
• Use of any investigational medication for treatment of cancer in a clinical study within the past 30 days (must have completed all investigational treatments and corticosteroids and be receiving only outpatient, non- investigational maintenance chemotherapy).

Other illness

• Heart rate ≥120 bpm on 3 separate occasions
• Participant currently uses, or has used in the past 3 months, other stimulants/sympathomimetic amines (for attention deficit/hyperactivity disorder (ADHD )or other indication).
• Participant has a health condition that interferes with metabolism (untreated hypothyroidism, growth hormone deficiency with or without treatment, hypothalamic obesity).
• Participant has epilepsy requiring anticonvulsants for seizure management.
• Participant has any history of eating disorder or laxative abuse.
• Participant has a history of substance abuse.
• Participant has relapsed disease or need for transplant.

Lab values

• Participant has diabetes mellitus (type 1 or 2 currently on medication or with Hemoglobin A1c ≥6.5%). Participants with a history of steroid induced diabetes requiring insulin who are no longer meet criteria for diabetes, are off any insulin for the past 3 months and have no further planned steroid exposure are eligible.
• Participant has significant cardiac disease or ECG abnormality including:
  • corrected QT interval (qTC) prolongation \>460msec, congenital heart disease with significant repair, cardiac arrhythmias requiring medication or pacemaker, heart failure requiring medication or uncontrolled hypertension or tachycardia.
• Participant has renal dysfunction (eGFR \<60 mL/min), bicarbonate \<18meq/L (labs may be repeated per investigator discretion), history of nephrolithiasis.
• Participant has clinically significant liver disease (AST or ALT \>3-times upper limit of normal, lab may be repeated per investigator discretion).

Age

• Participant has poorly controlled hypertensions: current blood pressure
  • 140/90 on 3 separate occasions (and for age 12 \> 95th percentile on 3 separate occasions) or recent change in anti-hypertensive medication that has not been stable for 3 months
• Participant has a genetic or other congenital condition involving global delays (i.e.Trisomy 21, cerebral palsy) or requires a surrogate for over age 18 years.
• Non-English speaking participant (or primary guardian/caregiver for those \<18 years).

Other

• Participant has had recent, ongoing weight loss (≥5 kg in past 3-months).
• Participant is pregnant, planning to become pregnant or breast feeding.
• Participant is unable to swallow pills.

• Participant has acute lymphoblastic leukemia (ALL), Hodgkin lymphoma, or non-Hodgkin lymphoma.
• Participant has achieved remission and is completing outpatient, maintenance therapy with no further planned inpatient therapy and no use of experimental or investigational treatment OR participant is up to 27 months off therapy (to allow patients who return for 2 year off therapy visits slightly beyond the time point to remain eligible).
• Participant will have completed all cycles of therapy that include corticosteroids at the time of study
• Participant is age ≥12 and \<25-yrs at study entry
• Participant has obesity (BMI ≥95th percentile for age- and sex- or BMI ≥30 kg/m2, whichever threshold is lower).
• Participant must provide written informed consent (if ≥18 years) or assent if 12-\<18 years and, if age \<18 a parent or legal guardian must provide consent and willingness to accompany subject to study visits.
• If female, participant must be using or willing to use adequate contraception defined as one of the following: double barrier methods, hormonal contraception plus single barrier method, tubal ligation or abstinence.