Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial.

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy.

Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: Report of CALGB 361006 (Alliance).

Objective: To demonstrate feasibility of performing geriatric assessment (GA) in the National Clinical Trials Network (NCTN) and to explore the utility of GA to characterize treatment tolerance.

Materials And Methods: We conducted a multisite companion study (CALGB 361006) to CALGB 11001, a phase 2 trial of adults ≥60 years old with newly diagnosed FLT3- mutated AML, testing the efficacy of adding sorafenib to intensive chemotherapy. On 361006, a GA was administered prior to induction and prior to post-remission therapy.

A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403.

Retrospective studies have suggested that older adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) have better survival rates when treated using a pediatric ALL regimen administered by pediatric treatment teams. To address the feasibility and efficacy of using a pediatric treatment regimen for AYA patients with newly diagnosed ALL administered by adult treatment teams, we performed a prospective study, CALGB 10403, with doses and schedule identical to those in the Children's Oncology Group study AALL0232. From 2007 to 2012, 318 patients were enrolled; 295 were eligible and evaluable for response.

Management of recurrent prostate cancer after radiotherapy: long-term results from CALGB 9687 (Alliance), a prospective multi-institutional salvage prostatectomy series.

Background: To evaluate efficacy and morbidity prospectively in a contemporary multi-institutional salvage radical prostatectomy (SRP) series.

Methods: Forty-one men were enrolled between 1997 and 2006, who suffered biopsy-proven recurrent prostate cancer (CaP) after receiving ≥ 60c Gy radiation as primary treatment for cTNM disease. Surgical morbidity, quality of life, biochemical progression-free survival (BPFS) and overall survival (OS) were evaluated.

Application of multi-state models in cancer clinical trials.

Background/aims The goal of this article is to illustrate the utility of multi-state models in cancer clinical trials. Our specific aims are to describe multi-state models and how they differ from standard survival methods, to illustrate how multi-state models can facilitate deeper understanding of the treatment effect on multiple paths along the disease process that patients could experience in cancer clinical trials, to explain the differences between multi-state models and time-dependent Cox models, and to briefly describe available software to conduct such analyses. Methods Data from 717 newly diagnosed acute myeloid leukemia patients who enrolled in the CALGB 10603 trial were used as an illustrative example.

Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update.

Background: The randomised phase 2 CABOSUN trial comparing cabozantinib with sunitinib as initial therapy for advanced renal cell carcinoma (RCC) of intermediate or poor risk met the primary end-point of improving progression-free survival (PFS) as assessed by investigator. We report PFS by independent radiology review committee (IRC) assessment, ORR per IRC and updated overall survival (OS).

Patients And Methods: Previously untreated patients with advanced RCC of intermediate or poor risk by IMDC criteria were randomised 1:1 to cabozantinib 60 mg daily or sunitinib 50 mg daily (4 weeks on/2 weeks off).

A phase 2 study incorporating sorafenib into the chemotherapy for older adults with -mutated acute myeloid leukemia: CALGB 11001.

The Cancer and Leukemia Group B (CALGB), now part of the Alliance for Clinical Trials in Oncology, conducted a multicenter, single-arm, phase 2 study in patients ≥60 years with FMS-like tyrosine kinase 3 ()-mutated acute myeloid leukemia (AML). In this study, sorafenib was added to daunorubicin and cytarabine-based induction and consolidation chemotherapy and was also continued for 12 months of maintenance therapy. The primary end point of the study was overall survival (OS) at 1 year in the FLT3 internal tandem duplication (FLT3-ITD) cohort.

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation.

Background: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population.

Methods: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations.

Cabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN Trial.

Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria.

Long-term outcomes for newly-diagnosed multiple myeloma patients treated with pegylated liposomal doxorubicin and bortezomib: final results of CALGB (Alliance) 10301, a multicentre phase II study.

Long-term outcomes and updated clinical efficacy and safety data were evaluated for newly-diagnosed multiple myeloma patients treated on a phase II study of bortezomib and pegylated liposomal doxorubicin (PegLD). Out of 61 patients, the overall response rate was 57% and the near-complete/complete response rate was 7%. Patients aged ≥65 years old had a higher incidence of treatment-related ≥Grade 3 non-haematological toxicity (80% vs.

Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance).

Purpose: Zoledronic acid decreases the risk for skeletal-related events (SREs) in men with castration-resistant prostate cancer and bone metastases but its role earlier in the natural history of the disease is unknown. This phase III study evaluated the efficacy and safety of earlier treatment with zoledronic acid in men with castration-sensitive metastatic prostate cancer.

Patients And Methods: Men with castration-sensitive prostate cancer and bone metastases whose androgen-deprivation therapy was initiated within 6 months of study entry were randomly assigned in a blinded 1:1 ratio to receive zoledronic acid (4 mg intravenously every 4 weeks) or a placebo.

A phase II study of the oral VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK222584) in myelodysplastic syndrome: Cancer and Leukemia Group B study 10105 (Alliance).

Background: Angiogenesis is implicated in the pathophysiology and progression of myelodysplastic syndromes (MDS). Vatalanib (PTK787/ZK222584; Novartis and Schering AG) inhibits receptor tyrosine kinases of vascular endothelial growth factor, platelet derived growth factor and c-Kit. We examined whether vatalanib induces hematological responses in MDS and/or delays progression to acute myeloid leukemia (AML) or death.

High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902.

Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate, was combined with high dose cytarabine (HiDAC; cytarabine 3g/m(2) over 3h daily for 5 days) for adults with relapsed or refractory AML. HiDAC plus GO 9mg/m(2) on day 7 and 4.5mg/m(2) on day 14 was not tolerated, but HiDAC followed by GO 9mg/m(2) on day 7 was safe: 12/37 (32%) patients with relapsed AML achieved complete remission.

Low-dose interleukin-2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720.

Purpose: Cancer and Leukemia Group B (CALGB) 9720 evaluated subcutaneous low-dose recombinant interleukin-2 (rIL-2) maintenance immunotherapy as a strategy for prolonging remission in older patients with acute myeloid leukemia (AML).

Patients And Methods: AML patients age 60 years and older in first complete remission after induction and consolidation chemotherapy were randomly assigned to no further therapy or a 90-day regimen of 14-day cycles of low-dose rIL-2, aimed at expanding natural killer (NK) cells, followed by 3-day higher doses aimed at activating cytotoxicity of expanded NK cells to lyse residual AML cells. All randomly assigned patients were included in an intention-to-treat analysis.

What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children's Cancer Group and Cancer and Leukemia Group B studies.

We performed a retrospective comparison of presenting features, planned treatment, complete remission (CR) rate, and outcome of 321 adolescents and young adults (AYAs) ages 16 to 20 years with newly diagnosed acute lymphoblastic leukemia (ALL) who were treated on consecutive trials in either the Children's Cancer Group (CCG) or the Cancer and Leukemia Group B (CALGB) from 1988 to 2001. CR rates were identical, 90% for both CALGB and CCG AYAs. CCG AYAs had a 63% event-free survival (EFS) and 67% overall survival (OS) at 7 years in contrast to the CALGB AYAs, in which 7-year EFS was only 34% (P < .

p53 protein expression status and recurrence in men treated with radiation and androgen suppression therapy for higher-risk prostate cancer: a prospective phase II Cancer and Leukemia Group B Study (CALGB 9682).

Objectives: It has been hypothesized that abnormal p53 protein expression is associated with a worse prognosis after radiation (RT) and androgen suppression therapy (AST). This hypothesis was prospectively tested.

Methods: Between May 1997 and April 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered on a study evaluating whether the endorectal magnetic resonance imaging (eMRI)-defined change in tumor volume (TV) during neoadjuvant (n) AST was associated with prostate-specific antigen (PSA) outcome.

Tumor volume changes on 1.5 tesla endorectal MRI during neoadjuvant androgen suppression therapy for higher-risk prostate cancer and recurrence in men treated using radiation therapy results of the phase II CALGB 9682 study.

Purpose: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST.

Patients And Methods: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered.

A phase II trial of cisplatin, fixed dose-rate gemcitabine and gefitinib for advanced urothelial tract carcinoma: results of the Cancer and Leukaemia Group B 90102.

Objective: To conduct a phase II trial to determine the efficacy of cisplatin, a fixed dose-rate infusion of gemcitabine and gefitinib (an orally active epidermal growth factor receptor tyrosine kinase inhibitor) in patients with advanced urothelial carcinoma.

Patients And Methods: Eligible patients had previously untreated measurable disease, an Eastern Cooperative Oncology Group performance status of 0-2 and creatinine clearance of >50 mL/min. The treatment regimen consisted of cisplatin 70 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, administered at a fixed dose rate of 10 mg/m(2)/min, given every 3 weeks concurrent with gefitinib 500 mg/day orally for a maximum of six cycles.

Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511.

CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations.

Prognostic significance of plasma scatter factor/hepatocyte growth factor levels in patients with metastatic hormone- refractory prostate cancer: results from cancer and leukemia group B 150005/9480.

Background: Scatter factor, also known as hepatocyte growth factor (SF/HGF), is a polypeptide growth factor thought to be important in the growth and spread of prostatic carcinoma.

Patients And Methods: Scatter factor/HGF levels in pretreatment plasma samples from 171 men with metastatic hormone-refractory prostate cancer enrolled in CALGB 9480 were quantified by solid-phase, enzyme-linked immunosorbent assay.

Results: The Cox proportional hazards model was used to assess the prognostic importance of SF/HGF with adjustment for established prognostic factors.

Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study.

Objectives: To test the hypothesis that chromogranin A (CgA) levels are prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC). The extent of neuroendocrine differentiation in prostate cancer correlates with aggressive disease and with progression to HRPC. Plasma CgA levels in patients with prostate cancer may reflect the extent of the tumor neuroendocrine phenotype.

The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480.

Unlabelled: Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)].