Currently Viewing:
Evidence-Based Oncology July 2017
Daratumumab With Standard Regimen Improves PFS, ORR Independent of Cytogenetic Risk in Multiple Myeloma
Surabhi Dangi-Garimella, PhD
Phase 1 Study Results at ASCO Support First-Line Use of Daratumumab in Multiple Myeloma
Surabhi Dangi-Garimella, PhD
Daratumumab-Based Combination Effective in Relapsed/Refractory Multiple Myeloma, Short PFS in Heavily Pretreated Patients
Surabhi Dangi-Garimella, PhD
Patient Selection Vital in Ensuring Improved Response to PD-1, PD-L1 Inhibitors in NSCLC
Surabhi Dangi-Garimella, PhD
An Early Stage Safety, Efficacy Study for Atezolizumab Plus Daratumumab in Advanced NSCLC
Surabhi Dangi-Garimella, PhD
LDH Levels Could Predict irAEs Associated With Checkpoint Inhibition and Radiotherapy in Lung Cancer
Surabhi Dangi-Garimella, PhD
Alectinib May Be a New Standard of Care for Treatment-Naïve ALK-Positive NSCLC
AJMC Staff
Dacomitinib a New First-Line Option for Advanced EGFR MutationŚPositive NSCLC
AJMC Staff
Androgen Deprivation, With or Without Radiotherapy, New Standard of Care in High-Risk Prostate Cancer
AJMC Staff
Trabectedin and Lurbinectedin Effective in BRCA2-Associated Metastatic Breast Cancer
AJMC Staff
HPV Vaccination May Lower Prevalence of Oropharyngeal Cancers in Young Adults
Surabhi Dangi-Garimella, PhD
Physical Activity, Healthy Diet Improve Survival in Colorectal Cancer: Study at ASCO
Surabhi Dangi-Garimella, PhD
Three Months of Oxaliplatin-Based Adjuvant Therapy Noninferior to 6 Months in Stage III Colon Cancer
AJMC Staff
Fas Biomarker Can Predict Response to Second-Line Therapy for Advanced Soft Tissue Sarcoma
AJMC Staff
Nivolumab, Alone or With Ipilimumab, Met the Disease Control Rate in Malignant Pleural Mesothelioma
AJMC Staff
Currently Reading
Ibrutinib vs No Consolidation Are Being Compared Following Autologous HSCT in IRONCLAD Trial
AJMC Staff
Physician, Regulatory, and Payer Perspectives on the Value of Real-World Data
Surabhi Dangi-Garimella, PhD
Do We Have Adequate Surveillance in Cancer Care?
Surabhi Dangi-Garimella, PhD
MACRA 2.0 and Beyond: Preparing Your Practice to Meet the Quality and Reporting Challenges
Surabhi Dangi-Garimella, PhD
ASCO Study Finds Shift in Diagnosis Stage for Several Cancers Following ACA Implementation
Surabhi Dangi-Garimella, PhD
Switching Study Reports Equivalence Between Filgrastim, Biosimilar in Breast Cancer
Surabhi Dangi-Garimella, PhD
Research Demonstrates Efficacy and Safety of Trastuzumab Biosimilar SB3
Kelly Davio
CT-P6, a Trastuzumab Biosimilar, Shares the Safety and Efficacy Profile of Its Reference
Kelly Davio
Can the 4 Ps Devise Interventions to Reduce the Financial Toxicity of Cancer?
Surabhi Dangi-Garimella, PhD
Adjuvant Chemotherapy Reduces Cost, Improves Survival in NSCLC Post-Surgery
Surabhi Dangi-Garimella, PhD
Brazilian Study Queries: Is NGS Cost-Effective in Advanced Lung Cancer?
Surabhi Dangi-Garimella, PhD
SEER-Medicare Database Analysis Notes Higher Resource Utilization Among Patients With Neuroendocrine Tumors
Surabhi Dangi-Garimella, PhD

Ibrutinib vs No Consolidation Are Being Compared Following Autologous HSCT in IRONCLAD Trial

AJMC Staff
A poster session at the 2017 American Society of Clinical Oncology Annual Meeting presented the trial details of IRONCLAD, a randomized phase 3 study of ibrutinib versus no consolidation following autologous hematopoietic stem cell transplantation for activated-B-cell subtype relapsed diffuse large B-cell lymphoma.
RELAPSED DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) in the rituximab era portends a poor prognosis: only approximately 25% of patients achieve long-term disease control following second-line therapy and autologous hematopoietic stem cell transplantation (auto HSCT). Further, patients with the relapsed/refractory activated–B-cell (ABC) subtype have a poorer prognosis at diagnosis than those with germinal center disease and are overrepresented at relapse.

A poster session at the 2017 American Society of Clinical Oncology Annual Meeting presented the trial details of IRONCLAD, a randomized phase 3 study of ibrutinib versus no consolidation following auto HSCT for ABC subtype DLBCL.1 The trial began in 2016 and final data collection for evaluation of the primary outcome measure, superior 24-month progression-free survival (PFS), will be in 2020.2

IRONCLAD is targeting disease pathobiology at the time of auto HCT in an effort to improve outcomes in ABC-DLBCL. Ibrutinib possesses a safety profile that allows it to be combined with cytotoxic chemotherapy and confers single-agent activity with a 37% response rate in patients with relapsed/ refractory ABC-DLBCL. The intergroup, randomized, placebo-controlled, phase 3 study combines ibrutinib or placebo with high-dose chemotherapy during conditioning with auto HCT and for the following 12 months. Patients with relapsed/refractory DLBCL undergo tissue resection and these samples are submitted centrally for real-time review and subtype assignment.

Eligibility criteria include no more than 3 prior regimens, no active central nervous system involvement, no need for long-term anticoagulation, and no progression with prior ibrutinib therapy. Patients with chemosensitive ABC-DLBCL are randomized to ibrutinib 560 mg or placebo with carmustine, etoposide, cytarabine, and melphalan (BEAM) or cyclophosphamide, BCNU (carmustine), and VP-16 (CBV) chemotherapy until day 0. After engraftment, patients receive ibrutinib 560 mg daily or placebo for 12 additional cycles. Patients with progressive disease on placebo will be eligible to cross over to ibrutinib monotherapy. An initial safety cohort of 6 patients is being enrolled to evaluate the tolerability of ibrutinib with concurrent BEAM and CBV therapy.

As previously stated, the primary endpoint is superior 2-year PFS (Ha/ H0 67% versus 50%). Secondary endpoints include time to count recovery, posttransplant response rates, overall survival (OS), PFS, and the incidence of secondary malignancies. PFS is defined as the proportion of patients who are alive and progression-free 2 years from randomization, using the Lugano classification.2 Secondary outcome measures include:2 
  • The incidence of hematologic toxicity of ibrutinib therapy in up to 60 months, summarized using contingency tables
  • The incidence of secondary malignancies in up to 60 months
  • The incidence of secondary malignancies, summarized using contingency tables
  • OS from randomization to death from any cause, assessed up to 60 months
  • For each arm, the distribution of OS will be estimated using the Kaplan-Meier method and will be compared between the 2 arms using the log-rank test and Cox regression method, adjusting for known predictors
  • PFS, from registration to disease progression or death, whichever comes first, in up to 60 months
  • For each arm, the distribution of PFS will be estimated using the Kaplan- Meier method. PFS will be compared between the 2 arms using the log-rank test and Cox regression method, adjusting for known predictors.
  • Response rate using the Lugano classification in up to 60 months. The metabolic response proportion following auto HCT will be compared between the 2 arms using the Chi-squared test
  • Time to hematopoietic engraftment (platelet count ≥20,000/mcL following nadir) from the first day of 1 week without platelet transfusion, assessed up to 60 months
  • Treatment-related mortality for up to 60 months, summarized using contingency tables
The prognostic and predictive role of a pretransplant fludeoxyglucose PET scan in the setting of ibrutinib or placebo therapy, the role of emergent B-cell antigen receptor pathway mutations, double-hit genetics, and pharmacogenetic determinants of treatment outcome and toxicities will be assessed in correlative studies. A total of 296 patients are expected to accrue over 4 years.

IRONCLAD is being undertaken by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), which was established to help meet a critical need for multi-institutional clinical trials that focus directly on improving survival for patients undergoing hematopoietic cell transplantation. Since 2001, the BMT CTN has opened more than 30 multi-institutional phase 2 and 3 trials, involved more than 100 transplant centers, and enrolled thousands of patients.3

BMT CTN is funded through the National Institutes of Health.
REFERENCES

1. Andreadis C, Fenske TS, Hill BT, et al. Ironclad: a randomized phase III study of ibrutinib (Ibr) or no consolidation following autologous hematopoietic stem cell transplantation (AutoHCT) for relapsed/refractory activated-B-cell (ABC) subtype diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2017;35(suppl; abst TPS7566).

2. Ibrutinib before and after stem cell transplant in treating patients with relapsed or refractory diffuse large B-cell lymphoma. ClinicalTrials.gov website. clinicaltrials.gov/ct2/show/NCT02443077. Updated June 27, 2017. Accessed June 30, 2017.

3. Blood and Marrow Transplant Clinical Trials Network. cibmtr.org/Studies/ClinicalTrials/BMT_CTN/pages/index. aspx. Updated June 14, 2017. Accessed June 30, 2017.
PDF
 
Copyright AJMC 2006-2017 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up
×

Sign In

Not a member? Sign up now!