EA4232 – A Randomized Phase III Study to Evaluate Benefits of Autologous Stem Cell Transplant in Patients with Peripheral T Cell Lymphoma who Achieved a First Complete Remission (CR1) Following Induction Therapy (PTCL-STAT)

The study chair for this trial is N. Nora Bennani, MD (Mayo Clinic). The study co-chairs are Marc S. Hoffmann, MD (The University of Kansas Cancer Center) for SWOG Cancer Research Network, Basem M. William, MD (OhioHealth) for the Alliance for Clinical Trials in Oncology, and Neil Chua, MD (University of Alberta/Cross Cancer Institute) for the Canadian Cancer Trials Group. The study co-chair for the Bone Marrow Transplant Clinical Trials Network is Jakub Svoboda, MD (University of Pennsylvania/Abramson Cancer Center). The community co-chair is Yazhini Vallatharasu, MD (ThedaCare).

Peripheral T-cell lymphoma (PTCL) is a rare and aggressive form of non-Hodgkin lymphoma that develops in mature white blood cells called T-cells and natural killer cells. There are several subtypes. The initial (induction) treatment is an anthracycline-based chemotherapy, the most common one being a four-drug regimen known as CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone). Prognosis in PTCL varies by subtype, stage, the presence of tumor gene mutations, and other factors. However, in general, PTCL is associated with a poor prognosis, and the overall five-year survival rate is only about 30-40 percent (National Cancer Institute).

Despite a high likelihood of induction therapy putting PCTL patients into remission, relapses are all too common. Thus, physicians will often recommend more treatment. Known as consolidation therapy, the goal is to eliminate any remaining cancer cells and keep the disease under control for as long as possible. Some physicians may offer an autologous stem cell transplant (ASCT)—if the patient is physically fit enough to withstand the difficult procedure, which involves high-dose chemotherapy followed by re-infusion of their own blood stem cells. However, the benefit of ASCT in these patients is heavily debated due to conflicting results from previous trials. Plus, ASCT has never been evaluated in a randomized controlled trial.

The EA4232 study is the first randomized phase 3 study to evaluate the benefits of consolidation treatment with high-dose chemotherapy and ASCT in patients with PTCL who are in complete remission following induction therapy.

All patients who participate in EA4232 must have already received treatment with an anthracycline-based chemotherapy regimen and be in complete remission (as measured by radiology imaging exams). After enrolling, they will be randomized to either the control arm (observation) or high-dose chemotherapy and ASCT. Both the ASCT procedure and the chemotherapy regimen will follow the standard practices of the hospitals and cancer centers participating in the trial.

Patients on the observation-only arm will undergo regular scans with PET-CT and CT imaging to monitor their condition. All patients will be followed for response until progression and for survival for 12 years from the date of randomization.

Additional treatment with high-dose chemotherapy and ASCT carries significant risks and side effects. If this trial finds that this therapy does not improve survival, then future patients will be spared unnecessary toxicity. If the trial finds that it does improve survival, then future patients and their physicians may be able to confidently consider it as a treatment option.  

This trial will also be exploring the impact of minimal residual disease on the benefit of ASCT. The findings will help to determine which subgroups have the best outcomes.

Learn more about EA4232 at ecog-acrin.org.