AHOD1721 (CA209744), Risk-based, response-adapted, Phase II open-label trial of nivolumab + brentuximab vedotin (N + Bv) for children, adolescents, and young adults with relapsed/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL) after failure of first-line therapy, followed by brentuximab + bendamustine (Bv + B) for participants with a suboptimal response.
Study ID: STU 012017-031
Ca209744 is a Phase 2, open-label study of n+Bv for children and young adults with relapsed/refractory cHL. Participants who do not achieve CMR after 4 cycles of n+Bv will receive Bv+B to help achieve CMR. There are 2 treatment cohorts: one with participants at low risk relapse (R1 cohort), and one with participants at standard risk relapse (R2 cohort). The start of the trial is defined as the first visit for the first screened participant. The end of the trial is defined as the last scheduled procedure shown in the Schedule of activities for the last participant. Study completion is defined as the final date on which data for the primary endpoint is expected to be collected.
1) Signed Written Informed Consent a) Participants must have signed and dated an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal participant care. b) Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study c) For participants unable to give their written consent, in accordance with local regulations, one or both parents, a guardian, or a legally acceptable representative must be informed of the study procedures and must document permission by signing the informed consent form approved for the study prior to clinical study participation d) Each participant must be informed about the nature of the study to the extent compatible with his or her understanding. Should a participant become capable or reach the age of majority, his or her consent should be obtained as soon as possible. The explicit wish of a participant who is a minor or unable to give his or her written consent, but who is capable of forming an opinion and assessing information to refuse participation in, or to be withdrawn from, the clinical study at any time should be considered by the investigator. e) Minors who are judged to be of an age of reason as determined by local requirements should also give their assent. The assent should be documented based on local requirements. Continued assent should be documented when important new information becomes available that is relevant to the participant[Single Quote]s assent. 2) Type of Participant and Target Disease Characteristics a) Participants must have measurable disease, documented by pathological and radiographic criteria i) Participants with pathologically confirmed cHL, excluding nodular lymphocyte-predominant HL, after failure or non-response to first-line therapy. (1). Relapsed disease is defined as achieving a CR to previous therapy but then progressing 3 months or more after completion of that therapy. (2). Refractory disease is defined as never achieving a CR to previous therapy or achieving a CR but then progressing within 3 months of completion of that therapy. ii) At least 1 measureable site of disease according to the Lugano 2014 criteria (International Working Group criteria). 70,71 iii) Participants must have FDG-PET-avid and bidimensional measureable disease of at least 1.5 cm in longest axis as documented by radiographic technique (CT preferred). b) Performance Level: Karnofsky >= 50 for participants > 16 years of age or Lansky >= 50 for participants <= 16 years of age (Appendix 5). Participants who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. c) Evaluable tumor tissue (archived or new biopsy) must be provided to the central laboratory as formalin-fixed paraffin-embedded (FFPE) tumor block or a minimum of 20 slides. In order to be treated, the sample must meet the minimum quality requirements, as determined by the central laboratory during the screening period. Note: Under special circumstances, if tumor tissue provided is deemed inadequate, contact the Medical Monitor for approval to begin treatment. 3) Age and Reproductive Status a) Males and Females, ages 5 to 30 years, inclusive b) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment c) Women must not be breastfeeding d) WOCBP must agree to follow instructions for 2 methods of contraception or complete abstinence (listed in Appendix 4) for the duration of treatment with investigational drugs (all IMPs) and for an additional 6 months post-treatment completion. e) Males who are sexually active with WOCBP must agree to follow instructions for 2 methods of contraception or complete abstinence (listed in Appendix 4) for the duration of treatment with investigational drugs (all IMPs) and for an additional 7 months posttreatment completion. In addition, male participants must be willing to refrain from sperm donation during this time. f) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, and still must undergo pregnancy testing as described in this section. 4) Physical and Laboratory Test Findings a) Screening laboratory values must meet the following criteria: i) Adequate bone marrow function defined as the following: (1).For participants without known bone marrow involvement: a. Peripheral absolute neutrophil count (ANC) >= 750/mm3 b. Platelet count >= 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment). Participants with known bone marrow metastatic disease will be eligible for study provided they meet the platelet counts following transfusion, however they will not be eligible for assessment of hematologic toxicity (2).For participants with known bone marrow involvement: a. Participants with cytopenias secondary to known bone marrow involvement are eligible regardless of ANC or platelet counts b. Participants may be enrolled and receive transfusions provided they are not known to be refractory to red cell or platelet transfusions. Participants with bone marrow involvement will not be evaluated for hematologic toxicity regardless of ANC or platelet counts at the time of diagnosis. ii) Creatinine clearance or radioisotope GFR >= 70 ml/min/1.73 m2 or a serum creatinine based on age/gender as follows: Age Maximum Serum Creatinine (mg/dL) Male Female 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 >= 16 years 1.7 1.4 iii) Adequate hepatic function as evidenced by the following: (1).Total bilirubin <= 1.5 x upper limit of normal (ULN) (2).SGPT (alanine aminotransferase [ALT]) <= 3 x ULN. For the purpose of this study, the ULN for SGPT is 45 U/L 5) Prior Anti-tumor Therapy a) Participants must have received first-line anti-cancer therapy that failed b) Participants must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy prior to signing consent. c) Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy. d) Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (eg, Neulasta) or 7 days for short-acting growth factor. For agents that have known AEs occurring beyond 7 days after administration, this period must be extended beyond the time during which AEs are known to occur. The duration of this interval must be discussed with the BMS Medical Monitor. e) Biologic (anti-neoplastic agent): At least 3 half-lives after the last dose of a biologic agent. f) Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody. g) Bleomycin: At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Martha Marie Pacheco
CHILDRENS ONCOLOGY GROUP OPERATIONS CTR