ALBERT

Description: T cells can be genetically modified to target tumor antigens through the expression of a chimeric antigen receptor (CAR). CAR T cells targeting the CD19 antigen is a novel therapeutic approach for patients with relapsed B cell acute lymphoblastic leukemia (B-ALL). We have previously demonstrated that CAR T cells have a significant clinical benefit in adult patients with relapsed B-ALL. The primary objective of this study (NCT01860937) is to extend the use and test the safety of CD19 specific CAR T cells in a multicenter trial for children and young adults with relapsed CD19+ B-ALL. To date, 24 patients with very high risk (VHR) or relapsed B-ALL have been enrolled on protocol with a median age of 12 years (range 2-20 years) at time of T cell collection. We have treated 9 patients with relapsed B-ALL with a median age 15 years (range 3-22 years) using patient derived T cells expressing a CD19 specific CAR (19-28z). Patients received a dose of 1-3 x 10^6 CAR T cells/kg and complete response (complete remission or complete remission with incomplete count recovery) occurred in 5/9 (55%) patients. Significantly, correlations with response included lower disease burden (as assessed by bone marrow cellularity; p20 fold), Flt-3L (〉55 fold), IL-5 (〉15 fold), IL-6 (〉100 fold), and IL-10 (〉15 fold) were demonstrated in patients with CRS. Monitoring of bone marrow demonstrated peak 19-28z CAR T cell detection within 1-2 weeks following infusion with gradual contracture over 1-2 months. These early results demonstrate the feasibility and significant clinical impact of this approach in patients with relapsed B-ALL. In an effort to more rapidly generate statistically relevant data, demonstrate the "exportability" of this technology between academic institutions, and offer this therapeutic option to a broader number of pediatric patients with chemo-refractory B-ALL we have expanded this trial to include a collaborating institution. The objective of our trial is not to provide an intent-to-treat cohort, but rather demonstrate the tolerability of this technology in patients with relapsed B-ALL. Furthermore, patients meeting disease eligibility were not pre-screened for lymphocyte function prior to collection and/or treatment. Subsequent cohorts of patients will receive 19-28z CAR T cells and will be evaluated for toxicity, persistence of CAR T cells, and for anti-leukemic efficacy. Disclosures Curran: Juno Therapeutics: Consultancy. Off Label Use: CAR T cells for B-ALL. Riviere:Juno Therapeutics: Other: Co-founder, stockholder and consultant. Prockop:Atara Biotherapeutics: Other: I have no financial disclosures, but Atara Biotherapeutics has exercised a licensing agreement with Memorial Sloan Kettering Cancer Center and MSKCC and some investigators at MSKCC have a financial interest in Atara.. Park:Actinium Pharmaceuticals, Inc.: Research Funding; Juno Therapeutics: Consultancy. O'Reilly:Atara Biotherapeutics: Research Funding. Sadelain:Juno Therapeutics: Other: Co-founder, stockholder and consultant. Brentjens:Juno Therapeutics: Other: Co-founder, stockholder and consultant.

Description: Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with “higher risk” acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 × 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/ or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P 〈 .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.

Description: The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m2 per day, cyclophosphamide 440 mg/m2 per day, and etoposide 100 mg/m2 per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care. This trial was registered at www.clinicaltrials.gov as #NCT00315705.

Description: Background: Clofarabine, a next generation nucleoside analogue, was well tolerated and demonstrated activity in adult and pediatric Phase I trials conducted in heavily pretreated leukemia patients. Multicenter Phase II studies in pediatric leukemia have completed accrual in the US and are reported here. Methods: Two Phase 2, multicenter, open-label studies were conducted with clofarabine in children with refractory or relapsed ALL or AML. Clofarabine was administered intravenously over 2 hours at 52 mg/m2/day for 5 consecutive days. Cycles were repeated every 2 to 6 weeks based on response and toxicity. Results: The studies enrolled 100 patients (60 ALL and 40 AML). Currently, data are available for 84 patients (49 ALL, 35 AML). Median age is 12 years (range 1 to 22 years) and median number of prior regimens is 3 (range 1 to 6). Thirty-nine percent had received prior bone marrow transplant (BMT). As determined by independent review, preliminary data indicate overall response rates of 31% in ALL (6 CR, 4 CRp, and 5 PR) and 26% in AML (1 CRp and 8 PR). Median duration of remission for ALL is 9.7 weeks (range 1.0 to 28.6) and for AML is 16.2 weeks (range 1.7 to 56.6+). Thirteen of 24 responding patients (54%) proceeded to BMT. Median survival was 42 weeks (range 7.0 to 63.1+) for responding ALL patients (CR+CRp+PR) and 39 weeks (range 7.7 to 93.6+) for responding AML patients (CRp+PR). Patients who failed treatment or were non-evaluable had shorter median survival; 7.4 weeks (range 0.9 to 40.1+) and 12.4 weeks (range 1.6 to 84.9+) for ALL and AML, respectively. Among the patients who were refractory to the last prior chemotherapy, 7/30 (23%) with ALL and 4/22 (18%) with AML achieved a response with clofarabine. Median duration of remission in these patients is 4.6 weeks (range 2.3 to 24.4+) for ALL and 20 weeks (range 1.7 to 56.6+) for AML. Most drug-related adverse events were transient including febrile neutropenia, diarrhea, nausea/vomiting, fever, skin rash, headache, elevation in liver enzymes and bilirubin, and infusion-related flushing and anxiety. Conclusions: Clofarabine is active as a single agent in pediatric ALL and AML that are refractory to intensive salvage regimens. The overall safety profile is similar to that reported in other pediatric salvage studies. Clofarabine in combination with standard chemotherapy is currently under investigation in children.

Description: Abstract 3546 Between August 1988 and December 2009, 40 pediatric patients (pts) received an allogeneic HSCT for the treatment of very high risk ALL in CR1. They were 22 males and 18 females, aged 0.8 –19.2 years (median 10.0). Thirty eight patients had very high risk features: high white cell count greater than 200,000/mm3 (N=7), hypodiploidy (N=6), including double hypodiploidy (N=3), high risk cytogenetics with t(9;22) (N=14) or Mixed Lineage Leukemia (MLL) (N=3), and induction failure (N=23). Induction failure was defined morphologically by a single marrow aspirate revealing greater than 35% blasts by day +7 of induction, or greater than 5% blasts by day +14 or day +28 of induction. The remaining two patients included one infant ALL with a WBC 〉100,000/mm3 and one patient with ALL, Evans Syndrome and a prior CNS hemorrhage and fungal infection. Twenty two patients had one VHR feature while 16 patients had two VHR features. Patients received marrow or peripheral blood stem cell transplants from HLA-matched siblings (N=14) or volunteer unrelated donors (N=21) or unrelated double cord blood transplants (N=5). Unrelated donors were HLA-matched for 12 pts, but mismatched for nine pts at one (N=6) or two Class I antigens (N=3). All cord blood donors were matched at 4 or 5/6 HLA-antigens. Twenty three patients received T-cell depleted grafts following cytoreduction with hyperfractionated total body irradiation (HF-TBI) 1,375-1,500 cGy, Thiotepa (Thio) 5 mg/Kg/day × 2 and Cyclophosphamide (CY) 60 mg/Kg/day × 2. Grafts were marrow T-cell depleted with soy bean agglutinin and e-rosetting for 15 patients or peripheral blood stem cells T-cell depleted by CD34 selection and E-rosetting for 8 patients. Twelve pts received unmodified grafts following cytoreduction with a TBI-CY based regimen (N=8) or chemotherapy regimen (N=4). Five patients received double cord blood grafts following HF-TBI 1,375 cGY, Fludarabine 25 mg/m2/day × 3 and CY 60 mg/Kg/day × 2. Graft-versus-host disease (GvHD) prophylaxis for the BMT recipients included cyclosporine (CSA) + methotrexate or steroids, and for the cord blood recipients, CSA and mycophenolate mofetil. With a median follow-up of 11.1 years (range 0.6–21.9 yrs), the 10-year overall survival and disease-free survival of the entire cohort were 78% and 70% respectively, and 80% and 72% respectively when excluding the accidental death. Two recipients of T-cell depleted grafts suffered a graft failure (one early and one late), both of whom received a secondary T-cell depleted graft from a (different) mismatched related donor, engrafted and are alive and well. Two recipients of unmodified marrow grafts relapsed 4.9, and 18.9 months post BMT, one of whom is still alive disease free following treatment with chemotherapy. One recipient of a double cord blood graft relapsed three months post transplant. The overall risk of relapse for the entire cohort was 15%. Six pts died; cause of death was: relapse (N=2), secondary malignancy (N=2), acute GvHD (N=1), and accidental death (head trauma) (N=1). Grade 2–4 GvHD was diagnosed in recipients of unmodified grafts (N=3), double cord blood graft (N=2) and T-cell depleted grafts (N=1). The OS and DFS for recipients of T-cell depleted transplants following TBI THIO CY were both 83% with a 0% relapse rate. In summary, the outcome of allogeneic HSCT for children with very high risk ALL in CR1 in our series appears to be superior to that reported with chemotherapy for patients with these very high risk features. Moreover, the use of hyperfractionated TBI, Thio and CY followed by T-cell depleted grafts from related or unrelated donors was associated with a very good outcome with no relapse and minimal GvHD. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1483 In Vitro culture reveals microenvironment-dependent growth, heterogeneity and hierarchical structure of primary human pediatric pre-B cell acute lymphoblastic leukemia (pre-B ALL) cells. J.-H. Shieh1, P. Steinherz2, J Shieh3 and M. A.S. Moore1. 1Moore Laboratory. Cell Biology Program and 2Leukemia and Lymphoma Studies, Department of Pediatrics, Memorial-Sloan Kettering Cancer Center, New York, NY. 3Department of Biology, Brandeis Univ., Waltham, MA Pre-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common leukemia in children. Although this pediatric pre-B ALLs are treatable, no in vitro nor in vivo models are available to investigate their pathophysiology other than a number of established cell lines that grow in the absence of any cytokine dependence or stromal interaction. To address this issue, we systemically evaluated the effects of various tissue culture parameters to the growth of primary pre-B ALL cells. A serum-free MS-5 cells (a murine bone marrow stromal cell line) co-culture system is capable of expanding the pre-B ALL CD34+CD19+ cells and supporting their differentiation to CD34−CD19+ B cells. This expansion requires a contact between the stromal cells and the pre-B ALL cells, and is inhibited by fetal bovine serum and IL-6 in a dose-dependent manner. c-Kit ligand and Flt3 ligand can reverse the IL-6 inhibition. Expansion of individual CD34+CD19+ cells revealed a hierarchical structure with respect to CD34 antigen expression and an heterogeneity in cell proliferation. When the pre-B ALL cells were sorted into CD34dim and CD34bright populations, the CD34dim cells were capable of a faster proliferation but gradually lost their CD34 antigen. In contrast, the CD34bright cells were more slowly proliferating and retained their CD34 antigen. We transduced the B-ALL cells with a fusion gene expressing green fluorescent protein (GFP) and luciferase (GFP-Lu-pre-B ALL). These GFP-Lu-pre-B ALL cells display the similar in vitro characteristics and in vivo xenograftment to NOD/SCID IL2R gamma null (NSG) mice as the non-transduced pre-B ALL cells. One hundred, 103, 104 or 105 GFP-LU-pre-B ALL CD34+ cells were i.v. transplanted to NSG mice. Both 104 and 105 cells resulted in the engraftment of the leukemia cells in limbs and cranium as judged by imaging after 6 weeks, and 103 cells engrafted after 13 weeks. When the 105 cells-transplanted mice were sacrificed after 14 weeks, the harvested peripheral blood, spleen (3–4×108cells/spleen) and bone marrow (5−10×106 cells/femur) displayed 2–3%, 51–55% and 75–81% of human CD34+CD19+ cells, respectively. Human CD34−CD19+ cells were 1–2%, 12–13% and 15–21%, respectively. Therefore, our stromal culture system supports leukemic stem cell/leukemia initiating cell proliferation and closely recapitulates the growth of primary human pre-B ALL cells in their niche in vivo, and reveals the heterogeneity and hierarchical structure of human pre-B ALL cells. The in vitro stromal co-culture system combined with the xenograft model of GFP-Lu-pre-B ALL cells provides powerful tools to dissect the pathophysiology of human pre-B ALL, and to screen new drugs for pre-B ALL therapy. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1514 Background: Outcomes for children with relapsed/refractory acute leukemia remain dismal. Clofarabine has been approved for the treatment of relapsed acute lymphoblastic leukemia (ALL). However activity in pediatric acute myelogenous leukemia (AML), and optimal combination chemotherapy regimens have yet to be established. We previously reported a 36% complete remission (CR) rate with gemcitabine in combination with topotecan, vinorelbine, and thiotepa (TVTG) in relapsed/refractory pediatric acute leukemias. In an effort to improve on the outcomes of TVTG, we substituted clofarabine for the gemcitabine to create the TVTC protocol. Methods: Following completion of a phase I study, a phase II trial of TVTC was conducted. Patients with relapsed/refractory ALL or AML were eligible. Patients were treated at the maximum tolerated dose (MTD) as determined from the preceding phase I study: clofarabine 40mg/m2/day IV × 5 days, topotecan 1mg/m2/day IV continuous infusion × 5 days, vinorelbine 20mg/m2/week IV × 3, and thiotepa 15mg/m2/day IV × 1 day. The primary endpoint was overall response rate (ORR), defined as CR or CR without platelet recovery (CRp). 17 patients were enrolled. The median age was 10 years (8 months – 24 years). 12 patients had AML, 4 had pre-B ALL, and 1 had biphenotypic leukemia. 13 patients had relapsed disease, and 4 had refractory disease. 2 of the 17 patients were inevaluable for response; one patient was enrolled with minimal residual disease positivity of leukemia, and one patient is currently undergoing therapy. Results: Of the 15 patients evaluable for response, the ORR was 73% (10 CR, 1 CRp). Among the 11 responders, 10 (91%) proceeded to stem cell transplantation. Of the 4 non-responders, 2 patients had no detectable leukemia in their follow-up marrow samples, but failed to have count recovery. The other 2 patients were refractory to therapy. 16 of the 17 patients were evaluable for overall survival (OS), as one patient is currently undergoing therapy. The OS of the 16 evaluable patients is 53%, with a median OS time of 16.2 months (1.5 – 57.7 months). The most common grade 3 or higher toxicities included febrile neutropenia (69%), transient transaminase elevation (50%), and catheter-related infection (44%). One of the patients died from cardiac arrest 45 days after beginning TVTC. There were no cases of VOD. Conclusion: TVTC demonstrates significant activity in patients with relapsed/refractory acute leukemia. Infectious complications occurred at similar rates to previously reported clofarabine combination studies. The activity seen in relapsed/refractory AML patients was very encouraging, with 8 of 11 (73%) evaluable patients achieving a CR/CRp. Given the high response and stem cell transplantation rates in relapsed AML patients on this study, patients with high risk de novo AML may benefit from incorporation of TVTC therapy into their treatment regimens. This regimen warrants further exploration in a larger cohort of relapsed leukemia patients. Disclosures: Off Label Use: Use of Clofarabine for patients with AML. Steinherz:Genzyme: Research Funding.

Description: Introduction: Despite improved outcomes for children with Hodgkin lymphoma (HL), relapsed and refractory disease remain a challenge for a subset of patients. High dose therapy followed by autologous stem cell transplantation (ASCT) is the standard of care for relapsed disease, largely based on data from studies in adults. As new therapies emerge for HL, risk stratification of pediatric patients with relapsed disease will be essential to determine which patients are likely to benefit from ASCT and which patients should be selected for alternative therapy. In this study we report the long-term outcome of 34 pediatric patients with HL who underwent ASCT at a single institution. Methods: We conducted a retrospective analysis of 34 consecutive pediatric patients with HL who underwent ASCT at Memorial Sloan Kettering Cancer Center from 1989-2013. Data collected included age, histology, treatment prior to ASCT, disease status at the time of transplant, conditioning regimen, and outcome after ASCT. Given recent data supporting a Childhood Hodgkin International Prognostic Score (CHIPS) for risk stratification in first-line therapy(Schwartz et al, ASH Abstract #3649, 2011), this score was calculated at the time of relapse to evaluate its prognostic relevance in the relapse setting. One point was awarded for each of the following: stage IV disease, bulky mediastinal adenopathy, albumin

Description: We have previously reported encouraging overall complete remission (CR) rates and an acceptable safety profile using the combination of clofarabine, cyclophosphamide and etoposide in relapsed or refractory childhood acute leukemia. Here, we report follow-up results of the phase I portion of the study and provide an update on phase II which is currently enrolling patients. Patients between 1 and 21 years of age with refractory or relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) (Phase I portion only) were enrolled. A standard 3+3 design was followed to determine the maximally tolerated dose combination in phase I. Five dosing cohorts evaluated escalating doses of clofarabine 20–40 mg/m2/day, etoposide 75–100 mg/m2/day and cyclophosphamide 340–440 mg/m2/day. All 3 study drugs were administered via IV infusion daily for 5 consecutive days in induction and 4 consecutive days in consolidation. Patients received up to 2 induction cycles, followed by consolidation (up to a maximum of 8 cycles in total). Dose-limiting toxicities in the phase I portion have been previously reported. The recommended phase II doses were clofarabine 40 mg/m2/day, cyclophosphamide 440 mg/m2/day, and etoposide 100 mg/m2/day. The phase II portion of the study is a single-arm open-label study with a planned total enrollment of 33 patients. Twenty-five patients (ALL: 20 patients; AML: 5 patients) were enrolled in the 5 phase I dose cohorts. The median number of prior induction regimens was 2, 7 patients (5 ALL, 2 AML) were refractory to their immediately preceding regimen, and 4 patients (1 ALL, 3 AML) had a prior hematopoietic stem cell transplant (HSCT). Based on investigator’s assessment, data showed complete remission (CR) in 10 patients (9 ALL, 1 AML) and complete remission without platelet recovery (CRp) in 6 patients (2 ALL, 4 AML) for an overall response rate of 64% (ALL: 55%; AML: 100%). Of the 16 responders (CR + CRp), 9 patients proceeded to HSCT after treatment. The median duration of remission (censored at the last known date of follow-up regardless of alternative therapy) for the 16 responders was 18.2 weeks (range 6.6 to 61.4 weeks) (ALL: median 31.4 weeks, range 6.6 to 61.4 weeks; AML: median 15.6 weeks, range 7.3 to 48.9+ weeks), including 31.4 weeks for the 10 patients with CR and 15.3 weeks for the 6 patients with CRp. At the last known date of follow-up, 7 of the 16 responders were alive and 4 of these remained in CR (three of these had undergone post-therapy HSCT). One patient with ALL completed 8 cycles of therapy, with a duration of remission of 61.4 weeks. In phase II, 3 of the first 8 ALL patients enrolled achieved a response (1 CR, 2 CRp). However, 4 patients developed severe hepatotoxicity (3 veno-occlusive disease, 1 hyperbilirubinemia). The study was amended to exclude patients with prior HSCT, viral hepatitis and/or cirrhosis, or elevated conjugated bilirubin levels. Four additional patients have since been enrolled in the amended phase II portion of the study and no cases of severe hepatotoxicity have been observed to date. In summary, the combination of clofarabine, cyclophosphamide and etoposide induced durable remission in children with relapsed or refractory acute leukemia. The recommended phase II doses of clofarabine, cyclophosphamide, and etoposide were 40 mg/m2/day, 440 mg/m2/day, and 100 mg/m2/day, respectively, each given for 5 days in induction. The phase II portion of the study is now actively enrolling patients with ALL without a history of prior HSCT following development of hepatoxicity in 4 patients. An update of all patients enrolled in phase II will be presented at the meeting.

Description: Background: Relapsed or refractory pediatric acute myeloid leukemia (AML) is an unfortunate reality in approximately 40% of children and young adults diagnosed with AML. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. Non-anthracycline based salvage regimens are crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a Clofarabine-based regimen with Topotecan, Vinorelbine, and Thiotepa (TVTC) in a cohort of patients with AML. Herein, we report on an expanded cohort of AML patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) since 2007. We report our center's experience using a Clofarabine-based regimen with Topotecan, Vinorelbine, and Thiotepa (TVTC), its overall response rate defined as complete remission (CR) and its use as a bridge to hematopoietic stem cell transplant (HSCT). Patients and Methods: All patients 10% bone marrow involvement, who were treated with the phase 2 recommended schedule of TVTC were included in this analysis. Patients received the TVTC regimen with Topotecan 1 mg/m2/day (120 hour continuous infusion, Days 0-4), Vinorelbine 20 mg/m2/dose (Days 0, 7, 14), Thiotepa 15 mg/m2/dose (Day 2), and Clofarabine 40 mg/m2/day (Days 3-7). The regimen could be administered without hospitalization in patients who did not require hospitalization for other reasons. Most patients received antimicrobial prophylaxis starting on Day 8 with Levofloxacin and fungal prophylaxis with either Posaconazole or Voriconazole. GCSF 5mcg/kg/day was initiated on Day 8. Bone marrow evaluation was performed at the point of hematologic recovery to assess response. Overall response rate (ORR) was defined as complete remission (CR) plus complete remission without platelet recovery (CRp). Results: A total of 29 patients with relapsed (n=19) or refractory (n=10) AML were treated since 2007. Eight patients (28%) had prior hematopoietic stem cell transplantation (HSCT). The ORR of the entire cohort was 59% (17/29). The ORR of patients with relapsed vs. refractory disease was 74% (14/19) and 30% (3/10), respectively. Seventeen of 29 patients (59%) received TVTC as a 1st re-induction regimen with 59% (10/17) of those patients achieving a CR/CRp. The remaining 12 patients had TVTC as 2nd or greater regimen with 58% (7/12) of those patients achieving a CR/CRp. Among the 17 total responders in the cohort, 13 (76%) proceeded to HSCT. Of those who proceeded to HSCT, 8 of 13 are alive today (62%). Median time since HSCT is 66 months (range 14 to 107 months). The most common adverse effects were febrile neutropenia in 20 out of 29 patients (69%) which was Grade 3 or less, 3 of 29 patients (10%) with Grade 4 or greater febrile neutropenia requiring ICU admission. One patient developed an abdominal mucormycosis infection. One patient developed bone marrow aplasia and died due to sepsis 45 days after receiving TVTC. Conclusions: TVTC is an active regimen for children and young adults with relapsed/refractory AML, with an acceptable toxicity profile . Non-anthracycline containing salvage regimens are especially important as patients usually receive 〉400mg/m2 daunorubicin equivalents during frontline therapy. The majority of responders were successfully bridged to HSCT without exposure to additional anthracycline, with approximately half of these patients demonstrating long-term survival. TVTC warrants further exploration as a re-induction regimen in a larger cohort of patients with relapsed/refractory AML. Disclosures Kobos: Janssen Research & Development: Employment.