Current Clinical Trials in Non-Hodgkin’s Lymphoma

The non-Hodgkin’s lymphomas (NHL) are the fifth mostcommon cause of cancer in men and women in the United States, and the fifth andsixth leading causes of cancer deaths, respectively. Approximately 54,000 newcases are projected to be diagnosed in the United States this year,[1] 25% to30% of which are indolent histologies, with the remainder being aggressivetumors.

Clinical Trials Referral Resource is designed to serve as a ready reference for oncologists to help identify clinical trials that might be suitable for their patients. We hope it will also enhance accrual to clinical trials by informing practicing oncologists of ongoing protocols. Currently in the United States less than 10% of eligible adult patients are entered into clinical trials. The result is a delay in answering important therapeutic and scientific questions and disseminating therapeutic advances to the general oncology community.

It should be emphasized that including a specific trial does not imply that it is more important than another trial. Among the criteria for selection are that the trial is addressing an important question and is not expected to close in the immediate future (less than 1 year), and that initial staging or laboratory tests required for patient eligibility are widely practiced and available. Information on other protocols can be accessed via Physician’s Data Query (PDQ).*

We emphasize that this is an attempt to encourage referral of patients to these trials. We are specifically not soliciting additional members for the cooperative groups, nor are we suggesting how practicing oncologists should be treating patients who are not in a study.

This month’s installment of Clinical Trials Referral Resource is devoted to current clinical trials in non-Hodgkin's lymphoma.

For patient entry information, see the individual trials.

* PDQ is a comprehensive database service provided by the National Cancer Institute’s International Cancer Information Center and Office of Cancer Communications for retrieval of cancer treatment information, including peer-reviewed statements on treatment options, supportive care, screening, and prevention; and an international clinical trials registry. For more information on PDQ, online access is available at www.cancer.gov/cancer_information/pdq/, or contact the Cancer Information Service offices (1-800-4-CANCER).

After decades of limited progress in the therapy of these disorders,therapeutic paradigms have undergone a revolution. This monumental change isclearly the result of the availability of rituximab (Rituxan), the firstmonoclonal antibody approved for the treatment of a human malignancy.[2,3]However, fewer than half of patients with follicular NHL respond to rituximab,and the median response duration is about 1 year. Potential means of improvingon this level of activity may be afforded by the new generation ofradioimmunoconjugates, notably ibritumomab tiuxetan (Zevalin), recently approvedby the Food and Drug Administration (FDA), and tositumomab/iodine-131tositumomab (Bexxar).[4,5]

Other cytokines, such as interleukin-12 (IL-12), may augment the effectorcell mechanisms activated when rituximab binds to the lymphoma cells.[6]Additional data suggest that bcl-2 antisense can potentiate the activity ofrituximab.[7]

Focus on Targeted Therapies

This month’s Patient Referral Resource in B-cell non-Hodgkin’s lymphomasmakes a resounding point that the current direction of clinical research hasmoved beyond minor modifications of the dose and schedule of standard,nonspecific cytotoxic approaches. The current focus is on specific, targetedtherapies. The rational development of new strategies that integrate multipleantibodies directed against different antigens, cytokines that enhance theactivity of those antibodies, antisense compounds, and new chemotherapy drugswith unique mechanisms of action will hopefully increase our ability to curethese patients.

The Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatmentand Diagnosis (DCTD) at the National Cancer Institute (NCI) sponsors a varietyof trials for patients with newly diagnosed non-Hodgkin’s lymphoma using awide range of agents and schedules. The list below includes approved and/oractive clinical trials that are currently being sponsored by the CTEP for thetreatment of non-Hodgkin’s lymphoma. Information about these studies can beobtained from the principal investigator or contacts listed for each trial orfrom Bruce Cheson, MD, at CTEP (ChesonB@ctep.nci.nih.gov),301-496-2522.

Phase III

Title: Randomized Trial of Patient-Specific Vaccination withConjugated Follicular Lymphoma-Derived Idiotype with Local GM-CSF in FirstComplete Remission
Protocol Number: NCI-00-C-0050, NCI-9900.v6
Participating Institutions: National Cancer Institute Medicine Branch,Moffitt Cancer Center and Research Institute, Northwestern University, DukeUniversity Medical Center, University of Pennsylvania Cancer Center, BellevueHospital Center
Contact: Larry W. Kwak, MD, Bethesda, Maryland, (301) 846-1607; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Title: Randomized Phase III Study in Low-Grade Lymphoma ComparingCyclophosphamide-Fludarabine to Standard Therapy Followed by MaintenanceAnti-CD20 Antibody
Protocol Number: E1496
Participating Institutions: Eastern Cooperative Oncology Group, Cancerand Leukemia Group B
Contact: Jean McDonald, Coordinator, Brookline, Massachusetts, (617)632-3610

Title: Phase III Randomized Study of Cyclophosphamide, Doxorubicin,Vincristine, and Prednisone (CHOP) With or Without Either Rituximab or Iodine I131 Tositumomab (Monoclonal Antibody Anti-B1) in Patients With Newly DiagnosedFollicular Non-Hodgkin's Lymphoma
Protocol Number: CLB-50102, SWOG-S0016
Participating Institutions: Southwest Oncology Group, Southwest OncologyGroup CCOP Ordering Group
Contact: Marjorie Godfrey, Coordinator, San Antonio, Texas, (210)677-8808; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Title: Phase III Study of Early High-Dose Chemoradiotherapy andAutologous Peripheral Blood Stem Cell Transplantation Versus Conventional DoseCyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patientswith Intermediate or High Grade Non-Hodgkin's Lymphoma
Protocol Number: CAN-NCIC-LY11, CLB-59903, E-S9704, SWOG-S9704
Participating Institutions: Southwest Oncology Group, Cancer and LeukemiaGroup B, Eastern Cooperative Oncology Group, National Cancer Institute of Canada
Contact: Marjorie Godfrey, Coordinator, San Antonio, Texas, (210)677-8808; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Phase II

Title: Pilot Study of Idiotype Vaccine and Epoch-Rituximab Chemotherapyin Untreated Mantle Cell Lymphoma
Protocol Number: 1033
Participating Institution: National Cancer Institute Medicine Branch
Contact: Wyndham H. Wilson, MD, Bethesda, Maryland, (301) 435-2415, wilsonw@mail.nih.gov

Title: Phase II Study of Rituximab and High-Intensity ChemotherapyWith Filgrastim (G-CSF) Support in Patients With Previously Untreated Burkitt'sLymphoma or Burkitt's Leukemia
Protocol Number: CLB-10002
Participating Institution: Cancer and Leukemia Group B
Contact: CALGB Central Office, Chicago, Illinois, (773) 702-9171
Latest Information:http://www.cancer.gov/clinical_trials/

Title: Phase II Study of Rituximab, Doxorubicin, Etoposide,Vincristine, Prednisone, and Cyclophosphamide in Patients With PreviouslyUntreated Aggressive CD20+ B-Cell Non-Hodgkin's Lymphoma
Protocol Number: CLB-50103
Participating Institution: Cancer and Leukemia Group B
Contact: CALGB Central Office, Chicago, Illinois, (773) 702-9171; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Title: Phase II Study of Intensive Chemotherapy and Rituximab WithAutologous Peripheral Blood Stem Cell Transplantation in Patients With MantleCell Lymphoma
Protocol Number: CLB-59909
Participating Institution: Cancer and Leukemia Group B
Contact: CALGB Central Office, Chicago, Illinois, (773) 702-9171; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Title: Phase II Randomized Study of Rituximab With or WithoutInterleukin-12 in Patients With B-Cell Non-Hodgkin's Lymphoma
Protocol Number: NCCTG-N0087
Participating Institution: North Central Cancer Treatment Group
Contact: Stephen M. Ansell, MD, Rochester, Minnesota, (507) 284-2511, ansell.stephen@mayo.edu; for a complete listing ofstudy contacts, click hereLatest Information:http://www.cancer.gov/clinical_trials/

Title: Phase II Study of High Dose Cytarabine/Methotrexate and HighDose Cyclophosphamide/Dexamethasone/Doxorubicin/Vincristine (HCVAD) in Patientswith Newly Diagnosed Diffuse and Nodular Mantle Cell Lymphoma
Protocol Number: MDA-DM-97200, NCI-T97-0101
Participating Institution: M. D. Anderson Cancer Center
Contact: Jorge E. Romaguera, MD, Houston, Texas, (713) 792-2933
Latest Information:http://www.cancer.gov/clinical_trials/

Phase I/II

Title: Phase II Study of Etoposide, Prednisone, Vincristine,Cyclophosphamide, and Doxorubicin (EPOCH) With Rituximab and Filgrastim (G-CSF)in Patients With Stage I-IV Non-Hodgkin's Lymphoma
Protocol Number: CRB-9307, NCI-93-C-0133L, NCI-MB-303, NCI-T93-0023N
Participating Institutions: National Cancer Institute Medicine Branch,Biological Response Modifiers Program, Massachusetts General Hospital,University of Maryland Cancer Center, Holy Cross Hospital
Contact: Wyndham H. Wilson, MD, Bethesda, Maryland, (301) 435-2415, wilsonw@mail.nih.govLatest Information:http://www.cancer.gov/clinical_trials/

Phase I

Title: Phase I Study of Rituximab Followed by Interleukin-2 inPatients With CD20-Positive B-Cell Lymphoid Malignancy
Protocol Number: NCI-130, OSU-0037, OSU-00H0223
Participating Institution: Ohio State University Hospital
Contact: Pierluigi Porcu, MD, Columbus, Ohio, (614) 293-4275, porcu-1@medctr.osu.eduLatest Information:http://www.cancer.gov/clinical_trials/

Title: Phase I Study of Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan,and Autologous Peripheral Blood Stem Cell Rescue in Patients With IndolentNon-Hodgkin's Lymphoma
Protocol Number: JHOC-J0004, NCI-970
Participating Institutions: Johns Hopkins University, Moffitt CancerCenter and Research Institute, Ohio State University Hospital
Contact: Ian W. Flinn, MD, Baltimore, Maryland, (410) 955-8781, iflinn@jhmi.eduLatest Information:http://www.cancer.gov/clinical_trials/

References:

1. Jemal A, Thomas A, Murray T, et al: Cancer statistics: 2002. CA Cancer JClin 52:23-47, 2002.

2. McLaughlin P, Grillo-López AJ, Link BK, et al: Rituximab chimericanti-CD20 monoclonal antibody therapy of relapsed indolent lymphoma: Half ofpatients respond to a four-dose treatment program. J Clin Oncol 16:2825-2833,1998.

3. Cheson BD: Rituximab: Clinical development and future directions. ExpertOpin Biol Ther 2:97-110, 2002.

4. Witzig TE, White CA, Gordon LI, et al: Final results of a randomizedcontrolled study of the Zevalin radioimmunotherapy regimen vs a standard courseof rituximab immunotherapy for B-cell NHL (abstract 3591). Blood 96:831a, 2000.

5. Kaminski MS, Zelenetz AD, Press OW, et al: Pivotal study of Bexxar (IodineI131 tositumomab) for chemotherapy-refractory low-grade or transformed low-gradeB-cell non-Hodgkin’s lymphomas. J Clin Oncol 19:3918-3928, 2001.

6. Ansell SM, Witzig TE, Kurtin PJ, et al: Phase I study of interleukin-12 incombination with rituximab in patients with B-cell non-Hodgkin’s lymphoma.Blood 99:67-74, 2002.

7. Auer RL, Corbo M, Fegan CD, et al: Bcl-2 antisense (Genasense) inducesapoptosis and potentiates activity of both cytotoxic chemotherapy and rituximabin primary CLL cells (abstract 3358). Blood 98:808a, 2001.