Nivolumab plus Doxorubicin, Vinblastine, and Dacarbazine for the Treatment of Pediatric, Adolescent, and Young Adult Patients with Early-Stage Non-Bulky Classic Hodgkin Lymphoma

Inclusion Criteria

• Age >= 2 year to 21 years
• Newly diagnosed early-stage (I/II) non-bulky (< 10cm) classical Hodgkin lymphoma
• Baseline ejection fraction must be > 40%
• Direct bilirubin < 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert’s disease or lymphoma involvement, in which case direct bilirubin < 3 x ULN will be considered eligible
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN unless considered due to lymphoma involvement, in which case AST and/or ALT < 5 x ULN will be considered eligible
• Creatinine clearance >= 30 mL/min unless related to disease
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent[s]), or an interval of 5 half-lives of the prior therapy (whichever is shorter). Steroids for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI)
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better as classified by PI
• Unless surgically or biologically sterile: Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months for males, and 6 months for females, after the last treatment * The effects of this combination of chemotherapy on the developing human fetus are unknown. For this reason, these agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy #CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: ** Postmenopausal (no menses in greater than or equal to 12 consecutive months) ** History of hysterectomy or bilateral salpingo-oophorectomy ** Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy) ** History of bilateral tubal ligation or another surgical sterilization procedure * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document as detailed below and if minor, getting parental/guardian consent

Exclusion Criteria

• Patients who have received prior systemic therapy for the lymphoma with the exclusion of steroids for inflammatory conditions (e.g. asthma) or greater than 72 hours of emergent steroids (e.g. symptomatic mediastinal mass)
• Patients who weigh less than 10kg
• Any severe allergy to any of the drugs (nivolumab [nivo]-AVD)
• Patients with any concurrent uncontrolled medical condition, infection, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment
• Patients who are receiving any other cancer directed investigational agents; the use of other chemotherapeutic agents or anti-lymphoma agents is not permitted during study
• Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• Current or prior use of immunosuppressive medication within 14 days prior to the first dose of nivolumab. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection). * The use of stable systemic steroid doses less than or equal to 20 mg of prednisone daily are permitted for medical conditions needing systemic steroids. * Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication)
• The use of strong inhibitors or inducers of CYP1A2 (dacarbazine interaction) or CYP3A4 (doxorubicin, vinblastine interactions) should be avoided. Multiple CYP3A4 interacting agents of moderate or strong effect in the HIV+ patients should not be used. This includes most HIV protease inhibitors
• Known active HIV and hepatitis B and hepatitis C (unless see below points [a][b]). Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Patients with prior hepatitis B and hepatitis C with are undetectable viral load are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Patients with a concurrent active malignancy under treatment
• Pregnant women are excluded from this study because these agents have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on protocol