Category: Clinical Trials

Obinutuzumab (GA101), a New Generation Rituximab

By Peter Martin, MD

Rituximab is a chimeric (human-mouse) monoclonal antibody directed against the protein CD20 on the surface of B-lymphocytes and most B-cell lymphomas. Several clinical trials have demonstrated that rituximab can increase response rates, prolong remissions, and improve survival among patients with various B-cell lymphomas and is an FDA-approved drug. Interestingly, rituximab was developed during an era when our understanding of how monoclonal antibodies might work was relatively naïve. Obinutuzumab (GA101) is a newer generation anti-CD20 antibody that has undergone significant engineering to capitalize on new knowledge. In preclinical testing, GA101 appeared to work better than rituximab. Three clinical trials evaluating GA101 in patients with follicular lymphoma were presented at the American Society of Hematology (ASH) meeting this year.

Dr. Gilles Salles presented the results of a phase I/II study performed in France, in which patients with indolent non-Hodgkin lymphoma (mostly follicular lymphoma). In phase I of the study, patients were treated with escalating doses of GA101, while in phase 2, patients were randomized between two dose levels (high-dose and low-dose). Most patients had received prior rituximab. Overall, GA101 appeared to be well tolerated, with mild infusion reactions being the most common side effect. The results were encouraging, particularly in the high-dose group, but will need to be confirmed with a larger study and longer follow-up.

Dr. John Radford presented the results of the international GAUDI study, which evaluated the safety and efficacy of combining GA101 with CHOP or FC chemotherapy in patients with previously treated follicular lymphoma. Continue reading “Obinutuzumab (GA101), a New Generation Rituximab”

ASH 2011: New Treatment for T-Cell Lymphoma

By Jia Ruan, MD

Update: The below mentioned trials are closed to enrollment. 

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of lymphoid diseases that constitute less than 15 percent of all non-Hodgkin lymphomas in adults in North America. The most common subtypes are 1) Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); 2) Anaplastic large cell lymphoma, primary systemic type (ALCL); and 3) Angioimmunoblastic T-cell lymphoma (AITL).  The PTCLs are generally aggressive, and tend to run a more relapsing and less favorable clinical course compared to B-cell NHLs.  Relapsed and refractory diseases are common. Novel and target therapies are in much need.

At the recent Annual Society of Hematology (ASH) meeting, Dr. Friedberg of the University of Rochester reported the result of a phase 2 trial of Alisertib (MLN8237), a potent inhibitor of aurora A kinase, in patients with relapsed aggressive non-Hodgkin’s lymphoma (NHL). Aurora kinases regulate mitosis during cell division. Inhibition of aurora A kinase can lead to mitotic errors and premature cell death. Alisertib is taken orally twice daily for 7 days on 21-day cycles. This phase 2 study enrolled a total of 48 patients, including 8 patients with peripheral T-cell lymphoma. The overall response rate was 32%.  Response in T-cell NHL was the most impressive at 57%: four out of eight patients responded, and the some of the responses were durable. The response rates in DLBCL and MCL were modest around 20%. Treatment-related side effects were generally tolerable and included low blood counts, fever, fatigue and inflammation in mouth. Based on these results, additional clinical trials (phase II sponsored by SWOG / NCI and phase III sponsored by Millennium) with this orally available compound are moving forward in T-cell lymphoma. Both of these studies will be available soon at Weill Cornell Medical College  (click here to read about the SWOG/NCI trial and click here to read about the Millennium trial on clinicaltrials.gov).

Dr. Advani of Stanford University discussed the updated results of an international phase 2 study of Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large cell lymphoma Continue reading “ASH 2011: New Treatment for T-Cell Lymphoma”

ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies

By Koen van Besien, MD, PhD

Allogeneic transplant can be curative for patients with lymphoma and is often effective in difficult situations where other treatments have failed. Unfortunately very few of us have suitable sibling donors and in a multi-ethnic society such as the US, finding HLA-identical donors in the transplant registry can also represent a challenge.  Several studies presented at the Annual Society of Hematology meeting offer evidence of rapid progress and increased success in the field of mismatched transplantation.  Dr. Symons from John’s Hopkins used mismatched related donors  ( also called haplo-identical donors i.e relatives who are partially HLA-identical) and with a novel chemotherapy regimen and  GVHD prophylaxis reported a low risk for graft vs host disease and excellent outcomes in patients with very high risk disease. Using similar technology even better results were reported by Dr. Bashey from Atlanta. He reported that the outcomes of such haplo-transplant were similar to those of transplants from HLA-identical siblings.  We used a slightly different approach and combined a haplo-identical transplant with an umbilical cord blood graft. In this procedure, the umbilical cord blood graft tends to assure long term hematopoiesis and may provide a more robust immune system with very little chronic graft vs host disease. We presented data on 51 patients with hematologic malignancies and the group from NIH used a similar approach to treat 10 pts with aplastic anemia. Both groups showed excellent rates of recovery and a high percentage of patients achieving prolonged remissions.  Dr. van Rood showed that the choice of umbilical cord graft may minimize the risk for disease recurrence.  It is too early to know which of these approaches, haplo or haplo-cord transplantation will ultimately become widely accepted, but the field is moving rapidly and options for patients who lack a sibling donor are rapidly improving.

Allogeneic transplantation for Hodgkin’s lymphoma

Though most patients with Hodgkin’s Lymphoma (HL) are cured with their initial treatment, a small percentage of them fail to achieve remission or relapse after initial treatment. Such patients usually receive a salvage chemotherapy regimen followed by autologous stem cell transplantation. However, only half of those undergoing autologous transplant are cured, and that percentage is even lower for those with incomplete responses to salvage. Using an innovative approach, Continue reading “ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies”