Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Ofatumumab

Patients who had negative baseline Bcl-2 in PB and BM will not undergo further treatment after radiotherapy; they will not repeat Bcl-2 during subsequent follow-up visits.

Patients who had positive baseline Bcl-2 in PB and / or BM and become negative after local radiotherapy will not undergo further treatment.

Patients who had positive baseline Bcl-2 in PB and / or BM and remain positive after local radiotherapy get Ofatumumab (8 weekly infusion of 1000 mg total dose).

Patients Bcl-2 negativized either after radiotherapy or after Ofatumumab, who became Bcl-2 positive during the follow-up monitoring will be treated/retreated with Ofatumumab 8 weekly infusions at the conventional dose of 1000 mg; Bcl-2 monitoring will be continued subsequently according to the program.In case of persistent positive PCR after Ofatumumab the treatment will not be repeated.

OFATUMUMAB

Alessandro Pulsoni, MD

Phase II prospective multicenter study for stage I/II Follicular Lymphoma treated with involved-field radiotherapy (IFRT) at doses of 24 Gy) with or without Ofatumumab for 8 weekly doses on molecular basis. Patients with positive basal Bcl-2 will be followed every 3 months and with Bcl-2 detection every 6 months for 3 years. Patient with negative basal Bcl-2 will be followed every 3 months without further Bcl-2 detection.

Ofatumumab treatment will be administered to:

1. Patients with positive basal PCR for Bcl-2-IgH rearrangement in BM and/or PB, resulting still positive after IFRT;
2. Patients with positive basal PCR for Bcl-2-IgH in

Stage I/IIA follicular lymphoma (FL) is considered a localized disease that can be adequately treated with radiotherapy alone. This strategy is recommended by the guidelines of the "Società Italiana di Ematologia" (SIE) and of the "European Society for Medical Oncology" (ESMO) The accurate definition of the truly localised forms represents a crucial issue in order to ensure an appropriate treatment design for such patients. The characteristic t(14;18) translocation, which leads to the over-expression of the Bcl-2 gene, is found in approximately 85% of FL; cells bearing this translocation can be detected in the peripheral blood (PB) or bone marrow (BM) by polymerase chain reaction (PCR).

PCR for the t(14;18) translocation provides a sensitive device to identify the presence of minimal non-Hodgkin lymphoma (NHL) cell contamination. Previous experiences have demonstrated that despite the limited stage, Bcl-2/IgH+ cells can be found at diagnosis in PB and/or BM of the majority of the patients. After treatment with local radiotherapy confined to the involved lymph node(s) only, disappearance of circulating Bcl-2/IgH+ cells in PB and/or BM was demonstrated in approximately 60% of positive patients. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was \<1:100 000.

Anti-CD20 monoclonal antibody treatment has clearly demonstrated, both alone and in combination with chemotherapy and radiotherapy, a high therapeutic potential in FL. A significant impact of treatment with the anti CD20 monoclonal antibody in reducing the minimal residual disease in FL has been demonstrated in several studies when used as consolidation or during the maintenance phase.

No data are currently available concerning the ability of anti-CD20 antibody treatment in reducing the proportion of Bcl-2 positive residual cells after radiotherapy in localized FL. The objective of this study is to take advantage of the therapeutic potential of anti-CD20 monoclonal antibody to reduce or eliminate minimal residual disease in patients with FL in localized stage (I/II) after conventional treatment with local radiotherapy of the involved site(s). The effectiveness of anti-CD20 monoclonal antibody treatment will be determined by the proportion of negativization of residual Bcl-2 positive cells after radiotherapy, evaluated by qualitative and quantitative PCR detection of viable Bcl-2/IgH rearranged cells in PB and/or BM.

"MIRO" Molecularly Oriented Immuno-radio-therapy

"MIRO" (Molecularly Oriented Immuno - Radio -Therapy): Multicenter Phase II Study for the Treatment of the Molecular Basis of Stage I / II Follicular Lymphoma With Local Radiotherapy With / Without Ofatumumab

The proportion of Bcl-2 negativization after Ofatumumab treatment will be estimated by the proportion, and its confidence interval, of residual Bcl-2 positive cases after radiotherapy, which will became negative after Ofatumumab treatment

Clinical response rate will be evaluated by the proportion and its confidence interval of patients achieving overall response (OR) complete response (CR) and partial response (PR).

Progression Free Survival (PFS) is defined as the length of time between the date of registration and the earliest date of disease progression or death due to any cause; If the patients doesn't not have a documented date of progression or death, the PFS will be censored at the date of last adequate assessment. Relapse Free Survival (RFS) is defined as the length of time between the achievement of Complete Remission (CR) and Relapse of disease

Relapse Free Survival (RFS) is defined as the length of time between the achievement of Complete Remission (CR) and Relapse of disease

Fondazione Italiana Linfomi - ETS

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

B-cell Lymphoma

Marginal Zone Lymphoma

Antirheumatic Agents

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

* A treatment cycle is defined as 28 consecutive days.
* Umbralisib will be administered at 800 mg by mouth once daily on days 1-28 of cycles 1-24.
* Rituximab will be administered at 375 mg/m2 by intravenous infusion on Cycle 1 Day 1 and may be administered at 375 mg/m2 by intravenous infusion or at 1400 mg by subcutaneous injection on days 8, 15, 22 of cycle 1, day 1 of cycles 2 to 6, then every 8 weeks starting on day 1 of cycle 7 until completion of 24 cycles of umbralisib (i.e. every other cycle for 18 cycles or 9 doses, for a total of 15 doses of rituximab), or until progression or intolerance.

Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive.

Umbralisib

Rituximab works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells

Jacob D. Soumerai, MD

This research is being done to assess Umbralisib and Rituximab as a first line therapy for Follicular Lymphoma or Marginal Zone Lymphoma.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved Umbralisib as a treatment for any disease.

The FDA has approved Rituximab as a treatment option for this disease.

Umbralisib is an investigational drug which blocks a protein called PI3K. PI3K is a protein that plays a role in the way cells grow. In this type of cancer, PI3K is increased and more active than usual. This helps the cancer cells to grow and survive. Early clinical trials have shown that Umbralisib can kill cancer cells in some patients and cause their tumors to shrink.

Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma

A Phase 2 Study of Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research

The frequency of patients who achieve a complete response

The frequency of patients who achieve a complete or partial response

The median progression-free survival using Kaplan-Meier method with time of registration as time origin.

The median overall survival using Kaplan-Meier method with time of registration as time origin.

The nature, frequency, severity, and timing of adverse events

TG Therapeutics

Massachusetts General Hospital

Principal Investigator

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants will be receive Ibrutinib as an oral capsule preparation once daily for a period of 2 years. The dose will be 560mg daily. Toxicities will be recorded and graded. Response to treatment will be determined by FDG-PET imaging every 6 months, or as clinically indicated, in conjunction with clinical assessment by a physician, including physical examination, every 4 weeks from day 1 (baseline) for the first 3 months and then every 3 months until the end of treatment at 2 years.

Ibrutinib will be administered orally, on a once daily continuous dosing schedule and in an outpatient setting. Treatment will continue for 2 years and there will be no planned treatment breaks. The dose of Ibrutinib will be initiated at 560mg per day, which will remain constant throughout the study period, unless otherwise specified.

Ariela Noy, MD

The purpose of this study is to find out how successful ibrutinib is at putting follicular lymphoma into full remission. In this study, remission will be determined by achieving a normal PET scan after treatment. A PET scan is an imaging test that looks for active lymphoma. People who don't have a complete remission on PET after their first treatment are at high risk for having their lymphoma return. This study will investigate if ibrutinib will help participants achieve a complete remission without giving additional chemotherapy. The study will also investigate any possible side effects of the study drug ibrutinib.

Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy

Protocol 20060 (PCYC): A Multicenter, Open-Label Pilot Study of Follicular Lymphoma Ibrutinib Consolidation for FDG-PET Positivity After Frontline Chemoimmunotherapy (FLIPP)

The primary objective is to determine the rate of conversion from FDG-PET positive to negative at 12 months from the start of ibrutinib in patients receiving at least 6 months of Ibrutinib consolidation therapy for follicular lymphoma achieving at least a PR but remaining FDG-PET positive after first line chemoimmunotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
"MIRO" Molecularly Oriented Immuno-radio-therapy	NCT02710643	Follicular Lymp... Follicular Lymp... Follicular Lymp...	OFATUMUMAB	18 Years -	Fondazione Italiana Linfomi - ETS
"MIRO" Molecularly Oriented Immuno-radio-therapy	NCT02710643	Follicular Lymp... Follicular Lymp... Follicular Lymp...	OFATUMUMAB	18 Years -	Fondazione Italiana Linfomi - ETS
Umbralisib and Rituximab as Initial Therapy for Patients With Follicular Lymphoma and Marginal Zone Lymphoma	NCT03919175	Lymphoma Follicular Lymp... Follicular Lymp... Follicular Lymp... Follicular Lymp... Marginal Zone L... Marginal Zone B...	Umbralisib Rituximab	18 Years -	Massachusetts General Hospital
Ibrutinib for Patients With Follicular Lymphoma Without Complete Response to Initial Chemoimmunotherapy	NCT02966730	Follicular Lymp... Follicular Lymp... Follicular Lymp... Follicular Lymp...	Ibrutinib	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for follicular lymphoma, grade 1