Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Follicular Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Rituximab

Immunoglobulins

Epratuzumab

Antineoplastic Agents, Immunological

Immunologic Factors

Induction Therapy (Month 1): Epratuzumab 360 mg/m\^2 by IV days 1, 8, 15 \& 22; Rituximab 375 mg/m\^2 by IV day 3, 8, 15 \& 22

Extended Induction (Weeks 12, 20, 28 \& 36) Epratuzumab 360 mg/m\^2 by IV weeks 12, 20, 28 \& 36; Rituximab 375 mg/m\^2 by IV weeks 12, 20, 28 \& 36

Days 1, 8, 15, 22 and weeks 12, 20, 28, \& 36: 360mg/sq m IV

epratuzumab

Day 3, 8, 15, 22 and weeks 12, 20, 28, \& 36: 375mg/sq m IV

rituximab

Barbara Grant, MD

RATIONALE: Monoclonal antibodies, such as epratuzumab and 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. Giving epratuzumab and rituximab together may be more effective in treating follicular non-Hodgkin lymphoma.

PURPOSE: This phase II trial is studying how well giving epratuzumab together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

OBJECTIVES:

Primary

* To determine the response rate (overall and complete) after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular non-Hodgkin lymphoma (NHL).
* To determine the time to progression after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.

Secondary

* To determine the toxicity profile of epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.
* To establish whether the therapeutic effects of the combination of epratuzumab and rituximab are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).
* To determine the relationship between the change in fludeoxyglucose F 18 uptake early after epratuzumab and rituximab treatment with response rate and time to progression.

OUTLINE:

* Induction therapy (month 1): Patients receive epratuzumab IV over 5-30 minutes on days 1, 8, 15, and 22 and rituximab IV on days 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
* Extended induction therapy (months 3, 5, 7, and 9): Patients receive epratuzumab IV over 5-30 minutes followed by rituximab IV in weeks 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.

Patients receive fludeoxyglucose F 18 (FDG) subcutaneously and undergo positron emission tomography at baseline and after induction therapy to assess the degree of FDG uptake.

After completion of study treatment, patients are followed every 4 months for 2 years then every 6 months for up to 10 years.

Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma

A Phase II Trial of Extended Induction Epratuzumab (Anti-CD22 Monoclonal Antibody) (CALGB IND #XXXXX) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma.

CR: complete disappearance of all detectable disease PR: \>=50% decrease in the sum of the product of diameters of indicator lesions

Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.

National Cancer Institute (NCI)

Alliance for Clinical Trials in Oncology

Induction Therapy (Month 1):

Epratuzumab 360 mg/m\^2 by IV days 1, 8, 15 \& 22; Rituximab 375 mg/m\^2 by IV day 3, 8, 15 \& 22

Extended Induction (Weeks 12, 20, 28 \& 36) Epratuzumab 360 mg/m\^2 by IV weeks 12, 20, 28 \& 36; Rituximab 375 mg/m\^2 by IV weeks 12, 20, 28 \& 36

Epratuzumab Plus Rituximab

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Complete Response

Partial Response

Number of Participants With Overall Response

Progression Free Survival

Percentage of participants who were alive at 3 years. The 3 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.

3-Year Overall Survival

Overall Study

Obinutuzumab

Obinutuzumab Injection \[Gazyva\] 1000mg flat i.v. on week 1, 2, 3, 4, 8, 12, 16; Low dose radiation Therapy (LDRT) involved site 2 x 2 Gy in week 9

Obinutuzumab Injection [Gazyva]

Low dose radiation Therapy (LDRT)

Klaus Herfarth, MD

Combined modality approach using Obitunuzumab and involved site low dose irradiation in early stage nodal follicular lymphoma. Radiation dose will be adapted for low-responders.

Primary Objective:

Evaluation of the rate of metabolic CR after low-dose involved site radiotherapy in combination with Gazyvaro (Obinutuzumab) in early stage nodal follicular lymphoma in order to avoid conventional full dose IF radiotherapy.

Secondary Objective:

Efficacy and safety of a response adapted radiation dose treatment schedule.

Extended field or total nodal irradiation had been the gold standard for early stage follicular lymphoma for a long time in Germany. An involved field (IF) irradiation has been favored due to the toxicity of large field irradiation in other countries (e.g. USA). However, smaller irradiation fields have been accompanied with an increased risk of recurrence. A combination of involved field irradiation with the anti-CD20 antibody Rituximab (MIR trial) has led to similar efficacy results compared to the large field irradiation but with markedly reduced side effects.

Haas et al. showed in a prospective trial, that a low dose radiation therapy (LDRT) can lead to a complete remission in up to 60% in follicular lymphoma. This is presumed to result from immune modulatory effects induced by LDRT. The effectiveness of LDRT could also be demonstrated in another prospective, randomized British trial (FORT trial: 2 x2 Gy vs. 12 x 2 Gy) with a CR rate of 40% after 2 x 2 Gy (60% after 12 x 2 Gy). Currently, it is unknown, which patients need a higher radiation dose and which not.

A metabolic complete remission (CR) is an important prognostic marker for progression-free survival. According to the results of the PRIMA trial, CR is a very strong predictive parameter if the CR is established using FDG-PET.

In the present GAZAI trial, patients with early stage nodular follicular lymphoma will be treated in a combined approach of immunotherapy with an anti-CD20 antibody and small field (involved site) irradiation as in the MIR trial. In GAZAI, the fully humanized anti-CD20 antibody Obinutuzumab (GAZYVARO) will be used, which showed a high efficacy in combination with bendamustin in patients with follicular lymphoma refractory to Rituximab (GADOLIN trial). In addition, the radiation dose will be limited to 2 x2 Gy in responding patients. A dose build-up to a total of 40 Gy (dose in the MIR trial) will be performed in case of failure to achieve a complete CR based on a FDG-PET in week 18.

Primary endpoint of the trial is the rate of CR (based on FDG-PET/CT) after Obinutuzumab and 2x2 Gy IS radiotherapy in week 18. Secondary endpoints are the morphological CR rate in week 7, week 18 and month 6, the PFS, the toxicity, the recurrence rate, the recurrence pattern, overall survival and quality of life.

Open, non-controlled, national multi-center phase II trial

Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma

Therapy of Nodal Follicular Lymphoma (WHO Grade 1/2) in Clinical Stage I/II Using Response Adapted Involved Site Radiotherapy in Combination With Gazyvaro

rate of metabolic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining PET positive lymphoma

rate of morphologic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining lymphoma

Relapse pattern (e.g. out-field or in-field) of all relapses

QoL according FACT-Lymph25 questionnaires

Roche Pharma AG

Heidelberg University

Principal investigator

Molgramostim

Sargramostim

sargramostim

gene expression analysis

gene rearrangement analysis

polymerase chain reaction

polymorphism analysis

laboratory biomarker analysis

Jean-Francois Rossi, MD, PhD

RATIONALE: Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. 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. Giving GM-CSF together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

OBJECTIVES:

Primary

* Evaluate the clinical efficacy of sargramostim (GM-CSF) and rituximab, in terms of overall objective complete and partial response rates, in patients with previously untreated follicular non-Hodgkin lymphoma.

Secondary

* Evaluate the time to progression in patients treated with this regimen.
* Evaluate the overall survival of patients treated with this regimen.
* Evaluate the duration of response in patients treated with this regimen.
* Evaluate the safety profile of this regimen in these patients.
* Evaluate the influence of FcγR polymorphisms on clinical response.
* Monitor FcγR-expressing cells in peripheral blood during treatment.
* Monitor the molecular biological marker bcl2 \[t(14;18)\] in peripheral blood and bone marrow.

OUTLINE: This is a multicenter study.

* Induction therapy: Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-5 and rituximab IV on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
* Maintenance therapy: Patients receive GM-CSF SC on days 1-5 and rituximab IV on day 1. Treatment repeats every 8 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples are collected at baseline and periodically during study for analysis of bcl2 rearrangement by PCR assay; FcγR expression by immunophenotyping; and FcγR polymorphisms.

After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.

GM-CSF and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma

An Open Label, Multicenter, Non Randomized Phase II Study to Evaluate Anti-tumor Efficacy and Safety of GM-CSF (Sargramostim, Leukine®) Associated With Rituximab (MabThera®) in Patients With Follicular Non Hodgkin's Lymphoma With no Prior Treatment

French Innovative Leukemia Organisation

Heart and Blood Diseases

Symptoms and General Pathology

Infections

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Recurrence

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Burkitt Lymphoma

Waldenstrom Macroglobulinemia

Plasmablastic Lymphoma

Lymphoma, Large-Cell, Immunoblastic

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphoma, Large-cell, Immunoblastic

Anti-Infective Agents

Micronutrients

Dermatologic Agents

Reproductive Control Agents

Anti-Inflammatory Agents

Anti-Dyskinesia Agents

Hematinics

Vitamins

Etoposide

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Leucovorin

Methotrexate

Prednisone

Vincristine

Cyclosporine

Cyclosporins

Tacrolimus

Etoposide phosphate

Bleomycin

Acyclovir

Interferons

Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim

Sulfamethoxazole

Immunosuppressive Agents

Interferon-alpha

Interferon alpha-2

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Doses and schedules of immunosuppressive drugs (cyclosporin (or FK506), prednisone, and acyclovir) will depend on whether patients are judged to have clinically urgent disease or not. Patients who do not have a CR after initial immunosuppression will receive 3 cycles (28 days each) Interferon alpha 2b at 3.0 x 10\^6 IU/m\^2 on days 1-28. Patients who have a CR will then receive 6 additional cycles with 3 doses per week, then go onto observation. Patients who do not have a CR will then receive a maximum of 6 21-day cycles of chemotherapy, consisting of: cyclophosphamide 650 mg/m\^2 on day 1, adriamycin 25 mg/m\^2 on day 1, etoposide 120 mg/m\^2 on day 1, prednisone 60 mg/m\^2 on days 1-14, cytosine arabinoside 300 mg/m\^2 on day 8, bleomycin 5 mg/m\^2 on day 8, vincristine 1.4 mg/m\^2 on day 8, methotrexate 120 mg/m\^2 on day 8, leucovorin 25 mg/m\^2 q 6 hours on days 8-9, G-CSF 5 ug/kg/day on days 2-14, and one double strength tablet trimethoprim-sulfamethoxazole 3 times per week.

bleomycin sulfate

recombinant interferon alfa

cyclophosphamide

cytarabine

doxorubicin hydrochloride

etoposide

methotrexate

dose varies during initial immunosuppression. During chemotherapy, 60 mg/m\^2.

prednisone

vincristine sulfate

Simple excision, for those patients who have resectable disease after initial immunosuppression.

conventional surgery

For treatment of localized disease that remains after initial immunosuppression.

radiation therapy

Lode J. Swinnen, MD

Leo I. Gordon, MD

RATIONALE: Reducing the amount of drugs used to prevent transplant rejection may help a person's body kill tumor cells. Giving biological therapy, such as interferon alfa, which may interfere with the growth of cancer cells, or combination chemotherapy, which uses different ways to stop tumor cells from dividing so they stop growing or die, may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of reducing immunosuppression, and giving interferon alfa and combination chemotherapy, in treating patients who have malignant tumors that develop after organ transplant.

OBJECTIVES: I. Evaluate the complete remission rate and survival of patients with lymphoproliferation following organ transplantation treated with a defined sequential approach: modification of immunosuppression, with surgery or limited radiotherapy for an isolated site of disease; interferon alfa; and chemotherapy (ProMACE-CytaBOM; cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate).

OUTLINE: All patients receive modification of immunocompetence, unless rejection is present at outset. These patients proceed directly to interferon treatment. Group 1 (see Disease Characteristics): Patients receive reduced doses of their current immunosuppressive therapy for 10 days. Group 2: Patients receive reduced doses of some of their current immunosuppressive therapy and discontinue some of the other therapy for 14 days. Immunosuppressive therapy then resumes on day 15. Immunosuppressive therapy continues throughout other therapy, unless otherwise noted. Some patients may then undergo surgery or radiotherapy. Interferon therapy: Patients receive interferon alfa (IFNA) subcutaneously or intramuscularly on days 1-28 for a maximum of 3 courses. Patients then receive maintenance therapy with IFNA 3 days a week for 4 weeks for up to 6 courses. Chemotherapy (ProMACE-CytaBOM): Immunosuppressive therapy is stopped on days 1-20. Patients receive cyclophosphamide IV, doxorubicin IV, and etoposide IV over 60 minutes on day 1, oral prednisone on days 1-14, and cytarabine IV, bleomycin IV, vincristine IV, and methotrexate IV on day 8. Treatment is repeated every 21 days for up to 6 courses. Patients with positive CSF cytology receive intrathecal methotrexate or cytarabine on days 1, 3, 5, 7, and 14. Some patients may continue this therapy on day 21 , then every 3 weeks for 5 doses, or may receive cranial irradiation. Patients are followed monthly for 1 year, every 2 months for 1 year, every 4 months for 1 year, then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 4-5 years.

SWOG-9239 Reduction of Immunosuppression Plus Interferon Alfa and Combination Chemotherapy in Treating Patients With Malignant Tumors That Develop After Organ Transplant

Phase II Trial of Sequential Modification of Immunosuppression, Interferon Alpha, and Promace-Cytabom For Treatment of Post-Cardiac Transplant Lymphoproliferation.

Eastern Cooperative Oncology Group

SWOG Cancer Research Network

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma	NCT00553501	Lymphoma	epratuzumab rituximab	18 Years -	Alliance for Clinical Trials in Oncology
Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma	NCT00553501	Lymphoma	epratuzumab rituximab	18 Years -	Alliance for Clinical Trials in Oncology
Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma	NCT03341520	Stage II Grade ... Stage II Grade ... Stage I Follicu... Stage II Follic...	Obinutuzumab In... Low dose radiat...	18 Years -	Heidelberg University
GM-CSF and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma	NCT00893477	Lymphoma	rituximab sargramostim gene expression... gene rearrangem... polymerase chai... polymorphism an... laboratory biom...	18 Years -	National Cancer Institute (NCI)
Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma	NCT00553501	Lymphoma	epratuzumab rituximab	18 Years -	Alliance for Clinical Trials in Oncology
SWOG-9239 Reduction of Immunosuppression Plus Interferon Alfa and Combination Chemotherapy in Treating Patients With Malignant Tumors That Develop After Organ Transplant	NCT00002657	Lymphoma Multiple Myelom...	bleomycin sulfa... recombinant int... cyclophosphamid... cytarabine doxorubicin hyd... etoposide methotrexate prednisone vincristine sul... conventional su... radiation thera...	15 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for stage ii grade 2 follicular lymphoma