NYMC623: A Comprehensive Risk-adapted Chemommunotherapy Protocol of Emerging Immunotherapies for Relapsed/Refractory Alk+ Anaplastic Large Cell Lymphoma (ACCELERATE)
New York Medical College
Summary
Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) high-risk ALK+ Anaplastic Large Cell Lymphoma (ALCL) have a low incidence of overall survival. This clinical trial will investigate if a new FDA approved medication called Nivolumab (NIVO) (which is a checkpoint blockade immunotherapy) combined with chemotherapy based on the patients risk status to get the patient into the best response possible. Then patients will receive lower doses of chemoimmunotherapy and allogeneic stem cell transplantation (stem cells from another person). The investigators this this new treatment will improve survival rates in this high-risk population of patients.
Description
Brief Background: A multitude of chemotherapeutic regimens have been evaluated for the treatment of de novo ALK+ ALCL. Unfortunately, no chemotherapeutic regimen has improved the 20-30% treatment failure rate. Given the ubiquitous cell surface expression of CD30 on ALK+ ALCL, the anti-CD30 antibody drug conjugate (ADC) brentuximab vedotin (BV) is a rational therapeutic agent for ALK+ ALCL. 16. In the most recent Children's Oncology Group (COG) trial for de novo ALK+ ALCL (ANHL12P1), BV was combined with ALCL99 chemotherapy and demonstrated the best reported outcomes with a 2-year event free su…
Eligibility
- Age range
- 1–39 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must weigh ≥10 kilograms at the time of study enrollment. * Patients with relapsed or refractory histologically or cytologically proven ALK-positive anaplastic large cell lymphoma meeting Low or High Risk Criteria: Low Risk Cohort (LR cohort): * Any patient with FIRST RELAPSE \> ONE YEAR from initial diagnosis of de novo ALK+ ALCL, * Common histology, * CD3 negative, AND * No prior exposure to vinblastine (VBL). High-Risk Cohort (HR cohort): * Any patient with RELAPSED OR PROGRESSIVE DISEASE less than ONE YEAR from initial diagnosis of de novo ALK+ ALCL, * S…
Interventions
- DrugVinblastine (Velban)
Low risk cohort patients will receive 2 cycles of Induction therapy with single-drug vinBLAStine (VBL), then undergo disease assessment. If complete remission (CR) and MRD -, LR patients will continue single-drug VBL for a total of 24 months (if absent disease progression or unacceptable toxicity).
- DrugBrentuximab vedotin (Adcetris)
HR cohort patients with no previous exposure to BV will receive 2 cycles of Induction therapy with BV and NIVO \[BV + NIVO\] one every 21 days, then undergo disease assessment. Patients in CR will proceed with consolidation with RTC allogeneic SCT (SCT)\*. If patient has any response other than CR and MRD-, they will receive 2 cycles of BV, VBL, and NIVO \[BV + VBL + NIVO\] once every 21 days
- DrugNivolumab (Opdivo)
High risk cohort patients with previous exposure to Brentuximab vedotin (BV) will receive 2 cycles of Induction therapy with VBL and NIVO \[VBL + NIVO\] on day 1 and 15, then undergo disease assessment. If response is not CR, or patient has PR/SD/PD, patient will receive \[BV+VBL+NIVO\] and subsequent therapy as defined for the HR2 cohort.
Location
- New York Medical CollegeValhalla, New York