New Clinical Trial: A Phase II Trial of PET-Directed Therapy for Limited Stage DLBCL

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with Diffuse Large B-cell Lymphoma (DLBCL). The study sponsor is the Southwest Oncology Group, and the principal investigator at Weill Cornell is Peter Martin, M.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 years and older
  • Patient must have biopsy proven diffuse large B-cell lymphoma
  • Patient cannot have received prior chemotherapy, radiation, or antibody therapy for lymphoma
  • Detailed eligibility reviewed when you contact the study team

Study Details 

This phase II trial studies how well PET-directed chemotherapy works in treating patients with limited-stage diffuse large B-cell lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Comparing results of diagnostic procedures, such as PET scan and CT scan, done before, during, and after chemotherapy may help doctors predict a patient’s response to treatment and help plan the best treatment.

Primarily, this study will assess the 5 year progression- free survival (PFS) rate in patients with newly diagnosed limited-stage diffuse, large B-cell lymphoma (DLBCL) using positron emission tomography (PET)/CT scan to direct therapy after 3 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP).

Patients will be stratified according to whether the patient was upstaged to advanced stage DLBCL, based on local review of the baseline PET/CT (yes vs no).

  • Chemotherapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV over 30-60 minutes, vincristine sulfate IV, and doxorubicin hydrochloride IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for 3* courses. NOTE: *Patients found to have advanced stage DLBCL based on local review of the baseline PET scan receive 6 courses of R-CHOP.
  • FDG/PET – Radiotherapy: Patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scan at baseline, on days 15-18 of course 3, and at 12 weeks after completion of course 3. Patients with complete response (PET scan negative) receive one additional course of R-CHOP as above. Patients with partial response (PET scan positive) undergo involved-field radiotherapy (IFRT) 5 days a week for approximately 4-5 weeks.
  • Monoclonal antibody: Beginning 3-6 weeks after completion of IFRT, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes and rituximab IV on day 1 and on day 7, 8, or 9.
  • Patients may undergo blood sample collection at baseline for correlative studies. Bone marrow tissue samples may be also collected for correlative studies.
  • After completion of study therapy, patients are followed up every 6 months for 2 years and then yearly for 5 years.

REDLAMP 4: Circulating Tumor DNA & CT Monitoring for Untreated DLBCL – A Correlative Biomarker Study

First-line chemotherapy for diffuse large B-cell lymphoma is given with curative intent, but is not always effective. In this video, Dr. Peter Martin discusses the implications of a recently published study in Lancet Oncology, which aimed to discover whether a blood test capable of detecting circulating tumor DNA might predict treatment success or failure. In the future, blood tests may be added to, or even replace, current standard surveillance methods like CT scans or PET scans.

Previous #REDLAMP entries can be viewed on our Youtube channel.

We encourage you to follow the Lymphoma Progam on Twitter, Youtube, and Facebook where we will highlight new videos are about research publications as they are released. We also welcome your feedback, suggestions and questions about this project. If you have other questions about our lymphoma program or clinical trials or would like to see one of our lymphoma specialists, please contact us at 646-962-2074.


New Clinical Trial: Phase 1 Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 in Relapsed or Refractory CLL and Lymphomas

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with mantle cell lymphoma. The study sponsor is Bristol-Myers Squibb Research & Development, and the principal investigator at Weill Cornell is John P. Leonard, M.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Hodgkin’s lymphoma or B-cell malignancy
  • Relapsed after, or refractory to, prior therapy for Hodgkin’s lymphoma or B-cell malignancy
  • Detailed eligibility reviewed when you contact the study team

Study Details 

This clinical trial is for men and women with relapsed or refractory lymphomas including:

  • Hodgkin
  • Follicular
  • CLL
  • DLBCL
  • Mantle cell lymphoma

The study is evaluating the experimental drug BMS-986016 (Anti-Lag-3), to demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to support further clinical testing.

The study will be conducted in 2 parts. Part A consists of a dose escalation design and Part B consists of cohort expansion in 4 disease-restricted populations. Treatment in Part B will be initiated when the maximum tolerated dose (or maximum administered dose) for Part A has been determined.

Subjects will complete up to 3 periods of the study: Screening (up to 28 days), Treatment (up to a maximum of twelve 8-week cycles of therapy), and Clinical Follow-up (135 days following last dose of study drug). Women of child bearing potential will have additional follow-up assessments through Day 165 for home pregnancy tests. Each treatment cycle comprises 4 doses of BMS-986016 administered intravenously on Days 1, 15, 29, and 43. Subjects will continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.


New Clinical Trial: Phase 2B Open-label, Randomized Two-arm Study of Selinexor with Low Dose Dexamethasone in Patients with Relapsed/Refractory DLBCL

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The study sponsor is Karyopharm, and the principal investigator at Weill Cornell is Peter Martin, M.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Pathologically confirmed DLBCL whose disease is relapsed and/or refractory with documented evidence of disease progression after the most recently administered chemotherapy regimen and who in the opinion of the investigator are not candidates for high-dose chemotherapy with stem cell rescue
  • Patients must have received at least 2 but no more than 4 prior multi-agent therapies
  • Detailed eligibility reviewed when you contact the study team

Study Details

This clinical trial is for men and women with Diffuse Large B-Cell Lymphoma (DLBCL) and were previously treated for this disease.

For patients who are not cured with front-line therapy, DLBCL is a very difficult disease to manage with only limited treatment options. Selinexor has demonstrated anti-tumor activity in heavily pretreated patients with various subtypes of DLBCL. This study is designed to confirm selinexor activity with relapse and/or refractory DLBCL in patients who have had at least two but no more than four prior multi-agent therapies and are not eligible for high dose chemotherapy with stem cell rescue at the time of study entry.

This is a randomized, two-arm, multicenter, open-label Phase 2b study of the selinexor high (100 mg) and selinexor low (60 mg) doses with low dose dexamethasone given orally to patients with relapsed/refractory DLBCL who have no therapeutic options of demonstrated clinical benefit. Two hundred patients (100 per arm) with relapsed/refractory DLBCL who meet eligibility criteria will be enrolled and randomized in a 1:1 ratio of high (100 mg) to low (60 mg) selinexor doses.


Dr. Peter Martin Explains a Recently Opened Trial Testing the Combination of Azacitidine Plus R-CHOP

In his words, Dr. Peter Martin, explains a recently opened phase 1 trial testing the combination of azacitidine plus R-CHOP in patients with high risk previously untreated diffuse large B-cell lymphoma (DLBCL) or grade 3B follicular lymphoma.

 


New Developments in Lymphoma – Winter 2015 Newsletter

The Lymphoma Program has published the winter 2015 edition of the New Developments in Lymphoma Newsletter.

Please look to this space for further announcements of future newsletter issues, or sign up for advance notice of the newsletter here.


Demethylase Activity of AID During Germinal B-cell Maturation Could Contribute to Lymphomagenesis

shaknovich_rBy Rita Shaknovich, MD, PhD

Diffuse large B-cell lymphomas (DLBCL) are aggressive tumors that arise from germinal center B-cells (GCB). Post GCB are noted for their heterogeneity and variable clinical outcomes. In previous genome wide studies we found profound alterations in the cytosine methylation patterning of DLBCL and that the expression of activation-induced deaminase (AID) was associated with the loss of methylation in DLBCL patients. AID functions as demethylase during embryonic development, which  led us to ask whether AID has demethylase activity during the transit of B-cells through the germinal center, and if over expression contributes to lymphomagenesis through the disruption of DNA methylation.

This question was addressed in an abstract during the 56th annual meeting of the American Society of Hematology (ASH). We studied the epigenetic function of AID in GCB and germinal center-derived lymphomas. Our preliminary results indicate that high AID expression is correlated with a more aggressive phenotype of the disease. We are currently analyzing the epigenetic targets of AID in both normal GCB and tumors, in order to find genes that could be epigenetically deregulated and contribute to the formation of lymphomas. These results demonstrate – for the first time – that AID functions as a demethylase in GCB in vivo. This suggests that the epigenetic role of AID could contribute to lymphomagenesis.


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