scholarly journals Marqibo®, Vincristine Sulfate Liposome Injection, for the Treatment of Advanced, Relapsed or Refractory Philadelphia Chromosome-Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) in an Adolescent Young Adult (AYA) Population

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1291-1291 ◽  
Author(s):  
Gary J Schiller ◽  
Lloyd E. Damon ◽  
Wendy Stock ◽  
Steven E Coutre ◽  
Pamela Hsu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Young Adult ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Adult Population ◽  
Philadelphia Chromosome ◽  
Phase 2 ◽  
Vincristine Sulfate ◽  
Phase 2 Study ◽  
The Us

Abstract Background: Patients aged 15 to 39 years old constitute the Adolescent Young Adult (AYA) population. In the US, leukemias represent ~6% of all cancers in this population with the incidence of Acute Lymphoblastic Leukemia (ALL) gradually decreasing with age as the incidence of acute and chronic myeloid leukemias (AML, CML, respectively) increase; ALL occurs at approximately twice the rate of AML in 15- to 19-year olds. Further studies are needed to define the unique features of leukemia in AYA patients, and to better assess and optimize treatment regimens. Marqibo®, vincristine sulfate liposome injection, uses a novel sphingomyelin and cholesterol nanoparticle that facilitates vincristine dose intensification without exacerbation of its toxicity, i.e., it has a wider therapeutic index than standard formulation vincristine. This formulation has also been shown to enhance the penetration and concentration of vincristine into tumors, and prolong plasma circulation time in non-clinical experiments. Marqibo is approved in the US for the treatment of adult patients with Philadelphia chromosome negative (Ph-) ALL in second or greater relapse, whose disease has progressed following two or more previous lines of therapy. We performed a retrospective analysis of data from the Phase 2 RALLY clinical trial (n=65) to examine the effects of Marqibo in the subgroup of the AYA population. The Phase 2 study results of the entire study demonstrated that treatment with single-agent Marqibo resulted in an Overall Response Rate (ORR) of 35%, with 20% of patients achieving a Complete Response (CR) or CR with Incomplete Blood Count Recovery (CRi) (O'Brien, S., 2012 J Clin Oncol). Methods: Data from the RALLY Phase 2 study of Marqibo were analyzed retrospectively to examine only the relapsed or refractory Ph- ALL patients 39 years of age and younger (n=44). In this study, Marqibo (2.25mg/m2) was administered via IV over 60 minutes without dose capping, once per week until response, progression, toxicity or hematopoietic transplant. Results: The median age of the 44 patients was 27 (range: 19-39), 57% were male, 82% had B-cell ALL and 18% had T-cell ALL. 84% had ECOG performance status of 0 or 1. The number of previous treatments ranged from 2-6. 41% had 2 prior lines of treatment, 41% had 3 prior lines of treatment, 16% had 4 prior lines of treatment and 2% had 6 prior lines of treatment. In addition, 59% of patients had previously received a hematopoietic cell transplant. The ORR in the AYA population was 39%, with 25% of patients achieving a CR or CRi. Overall, the safety profile of Marqibo was similar to that in the older adult population, with 35 (79.5%) patients having a treatment-related adverse event, of any grade, on study. The most common treatment-related adverse events, of any grade, in the AYA population were constipation (34%) and peripheral neuropathy (32%). Conclusions: Marqibo (vincristine sulfate liposome injection) was shown to have clinical benefit in AYA patients with relapsed or refractory Ph- ALL with similar safety and efficacy profiles compared to the entire adult population (range: 19-83). Disclosures Schiller: Sunesis: Honoraria, Research Funding. Damon:Atara: Consultancy; Sunesis: Research Funding; McGraw Hill: Other: Chapter Royalties; Sigms Tau: Research Funding. Stock:Gilead: Membership on an entity's Board of Directors or advisory committees. Coutre:Pharmacyclics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Douer:Gilead: Consultancy.

scholarly journals A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): Dose-Finding Results from the Part 1 Safety Phase

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 555-555 ◽  
Author(s):  
Sarah K. Tasian ◽  
Albert Assad ◽  
Deborah S Hunter ◽  
Yining Du ◽  
Mignon L. Loh
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 2 Study ◽  
Multi Agent

Abstract Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype occurring in 15-30% of older children and adolescents/young adults (AYAs) with B-ALL. Ph-like ALL is associated with high relapse rates and poor survival despite intensive multi-agent cytotoxic chemotherapy. Development of successful treatment strategies to decrease relapse and improve cure rates in patients with Ph-like ALL remains a major therapeutic gap. Rearrangements of cytokine receptor-like factor 2 (CRLF2-R) with frequent concomitant JAK2 point mutations occur in 50% of Ph-like ALL cases and induce constitutive JAK/STAT and other kinase signaling. An additional 15-20% of Ph-like ALL harbors other JAK pathway alterations, such as JAK2 or EPOR rearrangements, that similarly activate JAK/STAT signaling. Ruxolitinib is a potent, selective JAK1/JAK2 inhibitor with demonstrated activity in preclinical Ph-like ALL models and clinical safety as monotherapy in children with relapsed/refractory cancers. We report the initial safety of ruxolitinib in combination with post-induction chemotherapy in children and AYAs with newly-diagnosed high-risk (HR) Ph-like ALL with CRLF2-R or other JAK pathway alterations treated on the non-randomized, 2-part phase 2 study INCB18424-269 (AALL1521; NCT02723994). Methods: Patients aged 1-21 years at time of diagnosis with HR B-ALL and eligible Ph-like genetic lesions who had completed 4-drug induction chemotherapy as per the Children's Oncology Group (COG) AALL1131 study (NCT02883049) were eligible to participate. Patients were stratified into 4 cohorts by genetic alterations and end-induction flow cytometric minimal residual disease (MRD) status: cohort A = CRLF2-R JAK-mutant, MRD+; B = CRLF2-R JAK-wild-type, MRD+; C = other JAK pathway alterations, MRD+, D = any CRLF2-R or JAK pathway alteration, MRD-. Patients commenced treatment on the INCB18424-269/AALL1521 study at consolidation with ruxolitinib orally twice daily in combination with augmented Berlin-Frankfurt-Münster (aBFM) post-induction chemotherapy as per AALL1131. Five discontinuous dose levels (10-50 mg/m2/dose 14-days-on/14-days-off per cycle [DL-2 to DL2]) and one continuous DL1b (40 mg/m2/dose × 28 days per cycle) of ruxolitinib with aBFM chemotherapy were explored via a standard rolling 6 design. Dose-limiting toxicities (DLTs) were assessed through Day 29 of delayed intensification (DI) and defined as hematologic and non-hematologic toxicity with higher grade or more prolonged duration than observed in children with treated with identical chemotherapy (without ruxolitinib) on other COG HR B-ALL trials. Pharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted using serial blood samples obtained from patients during consolidation therapy. Results: Forty patients (pts) were enrolled in Part 1 (cohort A, n=10; B, n=9; C, n=5; D, n=16). Four patients discontinued study treatment before the Day 29 DI timepoint, 3 of whom were replaced. Patients had a median age of 14 years, and 67.5% were male. Treatment-emergent adverse events occurred in all patients and included anemia (75%), platelet count decrease and/or thrombocytopenia (65%), febrile neutropenia (72.5%), and AST or ALT increase (57.5%). Thirty-three patients had Grade 3/4 events deemed possibly related to ruxolitinib without identified DLTs. Eleven patients in Part 1 (27.5%) discontinued study therapy for various reasons: CNS relapse (2 pts), end-consolidation MRD+ (4 pts), multi-system organ dysfunction (MSOD; 2 pts), elective MRD- stem cell transplantation (1 pt), psychosocial/compliance issues (2 pts). One patient died of septic shock and MSOD not attributed to ruxolitinib. Preliminary analysis of plasma drug levels at 4 hours post-dose was consistent with the known PK profile of ruxolitinib. PD studies demonstrated dose-dependent inhibition of target phosphoproteins and, importantly, sustained inhibition of phosphorylated STAT5 with continuous ruxolitinib dosing at DL1b. Discussion: These findings demonstrate safety and tolerability of ruxolitinib in combination with intensive multi-agent chemotherapy in children and AYAs with newly-diagnosed HR CRLF2-R/JAK pathway-mutant Ph-like ALL and support continued investigation of treatment efficacy in Part 2 of this trial. Disclosures Tasian: Aleta Biopharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Incyte Corporation: Research Funding. Assad:Incyte Corporation: Employment, Equity Ownership. Hunter:Incyte Corporation: Employment. Du:Incyte Corporation: Employment.

scholarly journals Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia

2020 ◽  
Vol 4 (14) ◽  
pp. 3239-3245
Author(s):  
Ryan D. Cassaday ◽  
Kelsey-Leigh A. Garcia ◽  
Jonathan R. Fromm ◽  
Mary-Elizabeth M. Percival ◽  
Cameron J. Turtle ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Stevens Johnson Syndrome ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Measurable Residual Disease

Abstract The presence of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) confers a poor prognosis. CD19-targeted immunotherapy is effective against MRD but is logistically challenging, potentially toxic, and not applicable to T-cell ALL. We thus hypothesized that inhibition of PD-1 with pembrolizumab could also be effective for MRD, but without lineage restriction. The primary objective of this phase 2 study was to evaluate the efficacy of pembrolizumab in patients with ALL and MRD. Key eligibility criteria included adults with B- or T-cell ALL and MRD detectable by multiparameter flow cytometry or quantitative polymerase chain reaction from bone marrow aspirate (BMA) despite chemotherapy (plus ABL kinase inhibitor if Philadelphia chromosome positive). Pembrolizumab 200 mg IV was given every 3 weeks. Response was assessed by BMA using methods that previously detected MRD. The primary end point was complete MRD response rate. We stopped enrollment early; only 1 of 12 (8%) experienced a complete MRD response, which lasted 3 weeks. Interestingly, this patient had previously received hematopoietic cell transplantation and CD19-targeted chimeric antigen receptor–modified T-cell therapy and was the only patient to experience an immune-related adverse event from pembrolizumab (grade 3 Stevens-Johnson syndrome). Median overall survival from enrollment was 12.7 months. In summary, pembrolizumab had minimal activity against MRD but was generally well tolerated. These data can be compared with ongoing anti-PD-1 combination studies in ALL, and they further establish the role of trials specifically for patients with MRD. This trial was registered at www.clinicaltrials.gov as #NCT02767934.

Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2309-2315 ◽  
Author(s):  
Oliver Ottmann ◽  
Hervé Dombret ◽  
Giovanni Martinelli ◽  
Bengt Simonsson ◽  
Francois Guilhot ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Study Drug ◽  
Cytogenetic Response ◽  
Phase 2 ◽  
Effective Treatment Option ◽  
Imatinib Resistance ◽  
Phase 2 Study

Patients with Philadelphia (Ph) chromosome–positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015.

scholarly journals High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

2013 ◽  
Vol 31 (6) ◽  
pp. 676-683 ◽  
Author(s):  
Susan O'Brien ◽  
Gary Schiller ◽  
John Lister ◽  
Lloyd Damon ◽  
Stuart Goldberg ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chemotherapy Resistance ◽  
High Dose ◽  
Rapid Progression ◽  
Target Tissue ◽  
Vincristine Sulfate ◽  
Pivotal Phase

Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.

scholarly journals Pegaspargase Can Safely be Administered in Adults Age 40 and Older with Acute Lymphoblastic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3816-3816 ◽  
Author(s):  
Ryan J. Daley ◽  
Sridevi Rajeeve ◽  
Charlene C. Kabel ◽  
Jeremy J. Pappacena ◽  
Sarah E. Stump ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Board Of Directors ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hypersensitivity Reactions ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Frontline Treatment

Introduction: Asparaginase (ASP) has demonstrated a survival benefit in pediatric patients (pts) with acute lymphoblastic leukemia (ALL) and is now part of standard-of-care frontline treatment. As a result, asparaginase preparations have been incorporated into the treatment of adult ALL to improve outcomes. Pegaspargase (PEG-ASP), a modified version of asparaginase with prolonged asparagine depletion, appears to be safe in adults up to age 40 (Stock, et al., Blood, 2019), but is associated with a unique spectrum of toxicities, the risks of which appear to increase with age. Therefore, the safety of PEG-ASP remains a significant concern in older adults w/ ALL. Methods: We conducted a single center retrospective chart review of pts age ≥40 years who received PEG-ASP as part of frontline induction/consolidation or reinduction, between March 2008 and June 2018 at Memorial Sloan Kettering Cancer Center. The primary objective was to evaluate the tolerability and toxicity of PEG-ASP based on the incidence and severity of ASP-related toxicities (hypersensitivity reactions, hypertriglyceridemia, hyperbilirubinemia, transaminitis, pancreatitis, hypofibrinogenemia, etc) according to the Common Terminology Criteria for Adverse Events, version 4.03. Laboratory values recorded were either the peak or the nadir, the more appropriate for toxicity assessment, within a 4-week period following PEG-ASP administration. Secondary objectives were to determine the total number of doses of PEG-ASP administered in comparison to the number of doses intended, and to characterize the rationale for PEG-ASP discontinuation when applicable. Fisher's exact test was used to compare the incidence of PEG-ASP toxicities with respect to pt and treatment characteristics (regimen, age, BMI, gender, Philadelphia chromosome positive (Ph+) vs. Ph-, presence of extramedullary disease, PEG-ASP dose). P values were not adjusted for multiple comparisons. Results: We identified 60 pts with ALL (40 B-ALL and 20 T-ALL) who received at least one dose of PEG-ASP. Nine pts were Ph+. The median pt age at initiation of the treatment was 53, (range, 40 to 80), and 19 pts had a BMI ≥30 kg/m2. Forty-four pts received treatment for newly diagnosed ALL, and 16 pts for relapsed disease. Table 1 lists pt baseline characteristics. Among the 44 pts with newly diagnosed ALL, 27 pts received PEG-ASP as part of pediatric or pediatric-inspired regimens at doses of 2000 - 2500 units/m2, and 1 pt received a modified dose of 1000 units/m2 due to age. The remaining 16 pts received PEG-ASP at doses of 1000 - 2000 units/m2 for consolidation, per established adult regimens (ALL-2 and L-20; Lamanna, et al., Cancer, 2013). Grade 3/4 ASP-related toxicities with a >10% incidence included: hyperbilirubinemia, transaminitis, hypoalbuminemia, hyperglycemia, hypofibrinogenemia, and hypertriglyceridemia. Frontline treatment regimens in which PEG-ASP was used in consolidation cycles only (ALL-2, L-20) were associated w/ a lower incidence of hyperbilirubinemia (p=0.009) and hypertriglyceridemia (p<0.001) compared to those regimens that included PEG-ASP during induction (pediatric/pediatric-inspired regimens) (Table 2). Younger age (40-59 vs. ≥60 years) was associated with a greater risk of hypertriglyceridemia (p<0.001) and higher PEG-ASP dose (≥2000 vs. <2000 units/m2) was associated with a greater risk of hypertriglyceridemia and hypofibrinogenemia (p=0.002 and p=0.025, respectively). Thirty-eight pts (63%) received all intended doses of PEG-ASP. Six pts stopped PEG-ASP to proceed to allogeneic hematopoietic stem cell transplantation (5 in CR1, 1 in CR2), and 7 pts stopped for hypersensitivity reactions. Hepatotoxicity was the only ASP-related toxicity that led to PEG-ASP discontinuation occurring in 5 pts (hyperbilirubinemia, N=4; transaminitis, N=1). The total number of intended doses of PEG-ASP based on regimens used was 186, and 112 were administered. Conclusion: PEG-ASP was incorporated into the treatment of 60 adult ALL pts age ≥40, with manageable toxicity. Seven pts discontinued PEG-ASP due to hypersensitivity reactions and 5 discontinued due to hepatotoxicity, but other reported toxicities did not lead to PEG-ASP discontinuation and the majority of the pts completed all intended doses of PEG-ASP. This study suggests that with careful monitoring, PEG-ASP can safely be administered in adults ≥40 years of age. Disclosures Rajeeve: ASH-HONORS Grant: Research Funding. Tallman:UpToDate: Patents & Royalties; Oncolyze: Consultancy, Membership on an entity's Board of Directors or advisory committees; Delta Fly Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellerant: Research Funding; Tetraphase: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nohla: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioLineRx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; Biosight: Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; KAHR: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees. Geyer:Dava Oncology: Honoraria; Amgen: Research Funding. Park:Takeda: Consultancy; Allogene: Consultancy; Amgen: Consultancy; AstraZeneca: Consultancy; Autolus: Consultancy; GSK: Consultancy; Incyte: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy.

Design of the Hallmarq Trial, a Phase 3 Study of Vincristine Sulfate Liposome Injection (VSLI, Marqibo®) in Adults with Newly Diagnosed, Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4300-4300
Author(s):  
Steven R. Deitcher ◽  
Jeffrey A. Silverman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Pharmacokinetic Parameters ◽  
Multiple Time ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Phase 3 ◽  
Childhood All ◽  
Free Survival

Abstract Abstract 4300 Background: Adult acute lymphoblastic leukemia (ALL) is a lethal and fulminant disease and one distinct from childhood ALL. There are approximately 2400 new cases per year in the US; approximately 80% of these will be Philadelphia chromosome (Ph) negative. Despite remarkable success in treatment of childhood and adolescent ALL, adult ALL patients are underserved by existing treatment options as reflected by the poor survival rates and extremely poor outcomes in the relapsed setting. Complete response (CR) rates in the front-line setting range from 90% in patients <30 years old to 57% in patients >60 years old and 3-year disease free survival ranges from 47% to 12% respectively. The unmet medical need in adult ALL is most pronounced in those age 60 and older. VSLI was recently granted accelerated FDA approval as a single-agent for the treatment of adults with advanced, relapsed and refractory Ph-negative ALL and has successfully completed a Phase 2 trial as a component of multi-agent therapy. Trial Design: HALLMARQ (NCT01439347) is a Phase 3, multi-national, randomized study to evaluate the substitution of VSLI for standard vincristine (VCR) in the induction, consolidation, and maintenance phases of combination chemotherapy in the treatment of patients ≥ 60 years old with newly diagnosed Ph-negative ALL. The chemotherapy “backbone” utilized in this trial is modified from the Cancer and Leukemia Group B 8811 protocol. Asparaginase product usage is optional. The total duration of protocol-specified therapy is up to 24 months. VCR is dosed at 1.4 mg/m2 with a per dose cap at 2 mg. VSLI is dosed at 2.25 mg/m2without a dose cap. A protocol-specified dose reduction algorithm applicable to both VSLI and VCR will be used to minimize Grade 3 neurotoxicity while also facilitating continued dosing. Growth factors (e.g., granulocyte colony-stimulating factor) and bowel regimens (e.g., daily stool softener) are recommended and will be prescribed according to investigator preference and institutional guidelines. The primary endpoint is overall survival (OS) and the study is powered for superiority. Secondary endpoints include remission rate, overall response rate, event-free survival, and safety and tolerability. Minimal residual disease (MRD) at multiple time points and pharmacokinetic parameters are being assessed. Conclusion: The HALLMARQ Trial will provide new insights into the frontline treatment of ALL in adults ≥60 years old as well as confirm the clinical benefit of VSLI monotherapy demonstrated in the Phase 2 RALLY Study that supported the initial product approval. HALLMARQ is based on a Special Protocol Assessment with the FDA and is currently enrolling. *On behalf of the HALLMARQ investigators. Disclosures: Deitcher: Talon Therapeutics: Employment, Equity Ownership. Silverman:Talon Therapeutics: Employment.

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