Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Behaviors and Mental Disorders

Rare Diseases

Lymphoma

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Aggression

Lymphoma, Large-Cell, Anaplastic

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Anaplastic Large Cell Lymphoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

rituximab

Cyclophosphamide, vincristine and doxorubicin as a drip into the bloodstream (intravenously) and prednisolone (steroid) as tablets taken with or after food.

CHOP regimen

cyclophosphamide

doxorubicin hydrochloride

prednisone

vincristine sulfate

Julie M Vose, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy plus rituximab is more effective than combination chemotherapy alone for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have newly diagnosed non-Hodgkin's lymphoma that has not been treated previously.

OBJECTIVES: I. Determine whether the addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) increases the failure-free survival of patients with newly diagnosed, previously untreated, aggressive B-cell non-Hodgkin's lymphoma. II. Determine whether the addition of rituximab changes the toxicity profile attributed to CHOP chemotherapy in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, histology (diffuse small cleaved cell, diffuse mixed, and diffuse large cell vs immunoblastic large cell, mantle cell, and marginal zone), and risk group (low vs intermediate vs high). Patients enter one of two treatment arms: Arm I: Patients receive rituximab IV on day 1, followed by cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone for 5 consecutive days beginning on day 3. Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone daily for 5 consecutive days beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients will be followed for 3 years.

PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 3 years.

Combination Chemotherapy With or Without Rituximab in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma

A Phase III Randomized Trial of CHOP Chemotherapy Plus Rituxan (IDEC-C2B8) Versus CHOP Chemotherapy Alone for Newly Diagnosed, Previously Untreated, Aggressive Non-Hodgkin's Lymphoma

National Cancer Institute (NCI)

University of Nebraska

Infections

Heart and Blood Diseases

Recurrence

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma, Follicular

Hodgkin Disease

Burkitt Lymphoma

Waldenstrom Macroglobulinemia

Hematologic Diseases

Disease Attributes

Leukemia, B-Cell

Chronic Disease

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Chronic Graft Versus Host Disease

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Follicular Lymphoma

Hodgkin Lymphoma

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Fenretinide

Protective Agents

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

fenretinide

Ajay Gopal

This phase I/II trial is studying the side effects and best dose of fenretinide and to see how well it works when given together with rituximab in treating patients with B-cell non-Hodgkin lymphoma. Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving fenretinide together with rituximab may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To evaluate the safety of fenretinide delivered in a 5 of 7 day regimen. (Phase I) II. To estimate the efficacy (response rates) of fenretinide + rituximab in patients with B-cell non-Hodgkin lymphoma (NHL). (Phase II)

SECONDARY OBJECTIVES:

I. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase I) II. To determine the intratumoral concentrations of fenretinide. (Phase I) III. To evaluate the in vivo mechanism of action of fenretinide. (Phase I) IV. To identify the predictors of response to fenretinide. (Phase I) V. To estimate the response rates, positron emission tomography (PET) response, overall survival (OS), progression-free survival (PFS), time to progression (TTP), and disease-free survival (DFS) of patients treated on this study. (Phase I) VI. To estimate the overall survival (OS), progression-free survival (PFS), time to progression (TTP), disease-free survival (DFS), and PET responses of patients treated on this study. (Phase II) VII. To perform pharmacokinetic studies on patients receiving fenretinide. (Phase II) VIII. To determine the intratumoral concentration of fenretinide. (Phase II) IX. To identify the predictors of response to fenretinide and fenretinide + rituximab in B-NHL. (Phase II) X. To evaluate the in vivo mechanism of action of fenretinide in B-NHL. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of fenretinide followed by a phase II study.

PHASE I: Patients receive fenretinide orally (PO) twice daily (BID) on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab intravenously (IV) once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

A Phase I-II Trial of Fenretinide (4-HPR) + Rituximab in Patients With B-cell Lymphoma

A group of 3 patients would start treatment ast the dose of 900mg/m\^2 BID, and if none of the 3 experienced a DLT, another 3 would then be treated at that dose. Dose Limiting Toxicity was defined as any related toxicity of grade 4 or 5 on or before the completion of 4 weeks of therapy.

Per response evaluation criteria 1999 Cheson Response Criteria for Malignant Lymphoma (CHESON99) for target lesions assessed by either CT or MRI:

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; Complete Response Unconfirmed (CRU): Complete disappearance of all measurable and non-measurable disease, with the exception of all residual nodal masses \>1.5cm in Greatest Transverse Diameter (GTD) reduced by 75% in Sum of the Product of the greatest Diameters (SPD); Partial Response (PR): 50% decrease in the SPD.

The trial was stratified into rituximab-naïve and rituximab pre-treated patients, and the target response rates for these groups were expected to be 30% and 10%, respectively. The numbers reported below are subjects who achieved a response of partial response or better.

PHASE I: Patients receive fenretinide PO BID on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8. Treatment continues in the absence of disease progression or unacceptable toxicity.

pharmacological study : Correlative studies

rituximab : Given IV

fenretinide : Given PO

Fenretinide and Rituximab

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Ajay Gopal

7 participants were analyzed in the Rituximab Naive arm and 16 participants were analyzed in the Rituximab Pre Treated Arm.

Safety, in Terms of Dose-limiting Toxicity (DLT) of 2 Daily Doses of Single Agent Fenretinide (Phase I)

PHASE II: Patients receive fenretinide PO BID on days 1-5 in weeks 1-8 and rituximab IV once weekly in weeks 5-8.

Fenretinide and Rituximab (Rituximab Naive)

Fenretinide and Rituximab (Rituximab Pre Treated)

No subjects in Phase 1 met the DLT, therefore Phase II was conducted at 900mg/m2. Of the 32 subjects, 4 subjects were not evaluable for disease response (2 subjects in Phase 1 and 2 subjects in Phase 2).

Response Rates of B-Non-Hodgkin Lymphoma to the Combination of Rituximab and Fenretinide (Phase II)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Combination Chemotherapy With or Without Rituximab in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma	NCT00004112	Lymphoma	rituximab CHOP regimen cyclophosphamid... doxorubicin hyd... prednisone vincristine sul...	19 Years - 120 Years	University of Nebraska
Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma	NCT00288067	Adult Nodular L... B-cell Chronic ... Contiguous Stag... Contiguous Stag... Contiguous Stag... Contiguous Stag... Contiguous Stag... Contiguous Stag... Stage II Margin... Stage II Small ... Extranodal Marg... Nodal Marginal ... Noncontiguous S... Noncontiguous S... Noncontiguous S... Noncontiguous S... Noncontiguous S... Noncontiguous S... Recurrent Adult... Recurrent Adult... Recurrent Adult... Recurrent Adult... Recurrent Grade... Recurrent Grade... Recurrent Mantl... Recurrent Margi... Recurrent Small... Refractory Chro... Splenic Margina... Stage I Adult B... Stage I Adult D... Stage I Adult H... Stage I Adult L... Stage I Chronic... Stage I Grade 1... Stage I Grade 2... Stage I Small L... Stage II Adult ... Stage II Chroni... Stage III Adult... Stage III Adult... Stage III Adult... Stage III Adult... Stage III Chron... Stage III Grade... Stage III Grade... Stage III Mantl... Stage III Margi... Stage III Small... Stage IV Adult ... Stage IV Adult ... Stage IV Adult ... Stage IV Adult ... Stage IV Chroni... Stage IV Grade ... Stage IV Grade ... Stage IV Mantle... Stage IV Margin... Stage IV Small ... Waldenström Mac...	fenretinide rituximab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage ii marginal zone lymphoma