Ultra Low Dose Radiation Delivered Before or After Chemotherapy-Free Targeted Therapy in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Clinical Trial ID: NCT04054167

Description

This phase II trial studies how well ultra low dose radiation works before or after chemotherapy-free targeted therapy in treating patients with mantle cell lymphoma that has come back or does not respond to treatment. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Ultra low dose radiation is generally associated with a lower risk of side effects which may allow patients to be able to receive low-dose radiation therapy more often than high-dose radiation therapy. This trial may help doctors learn if giving ultra low dose radiation helps control mantle cell lymphoma and improves response to chemotherapy free targeted therapy.

PRIMARY OBJECTIVES: I. To evaluate the efficacy of adding ultra low dose radiation (ULDR) to chemotherapy free-targeted therapy (CTFTT) in contributing to a durable overall response in treated locations by estimating overall response rate (ORR) at 3 months. SECONDARY OBJECTIVES: I. To evaluate if ULDR can improve progression-free survival and overall survival. II. To evaluate the prognostic factors associated with inferior progression-free survival, including patient related and previous treatment related and if radiation can overcome these prognostic factors. III. To evaluate if radiation helps to bridge patients to other investigational drugs, by decreasing the disease bulk, controlling their symptoms, and maintaining a good performance status. OUTLINE: Patients undergo ultra low dose radiation for 1-2 days before chemotherapy free-targeted therapy. Patients may receive a second, longer course of radiation if the lesion treated does not respond. After completion of study treatment, patients are followed up every 6 months for up to 5 years.


Criteria

Inclusion Criteria: - Patients must have a confirmed diagnosis of mantle cell lymphoma with positivity in tissue biopsy. Biopsy does not need to be done of the lesions to be treated. - Patients must have previously treated relapsed and/or refractory mantle cell lymphoma (MCL) with at least 2 prior lines of therapy (prior carfilzomib, ibrutinib, bortezomib, anthracycline, rituximab or stem cell transplant are acceptable). There is no upper limit for prior lines of therapy. - Patients must have demonstrated progressive disease on positron emission tomography (PET)/computed tomography (CT) imaging following ibrutinib treatment, mono- or combinatorial therapy, in the relapsed/refractory setting. - Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form. - Patients must have bi-dimensional measurable disease (measurable disease by CT scan defined as at least 1 lesion that measures >= 1.5 cm in single dimension.) Patient presenting with lesions in the as at least 1 lesion that measures >= 1.5 cm in single dimension.) Patient presenting with lesions in the presence of leukemia phase (peripheral blood involvement), non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible. - Gastrointestinal or bone marrow or spleen only patients are allowable and will be analyzed separately. - Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. - Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty. - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and must be willing to use acceptable methods of birth control during the study and for 30 days after the last dose of study treatment. - Male patients must use an effective barrier method of contraception during the study and for 30 days following the last dose of study treatment if sexually active with a female of childbearing potential. - Serum bilirubin less than 1.5 mg/dl. - Creatinine (Cr) clearance greater than or equal to 30 mL/min. - Platelet count greater than 25,000/mm^3. - Absolute neutrophil count (ANC) greater than 1,000/mm^3. - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase SGOT) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase SGPT) less than 3 x upper limit of normal or less than 5 x upper limit of normal if hepatic metastases are present. - Patients who have bone marrow infiltration by MCL are eligible if their ANC is greater than or equal to 1000/mm^3 (growth factor not allowed) or their platelet level is greater than or equal to 25,000/mm^3. Exclusion Criteria: - Has had prior radiation therapy to the potential radiation target such that additional radiation therapy is considered unsafe by the treating radiation oncologist. - Has a diagnosis of active scleroderma or lupus or any other autoimmune disease that by the opinion of the treating radiation oncologist would put the patient at unacceptable risk of toxicity. - Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled infection, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. - Pregnant or breast-feeding females. - All patients with central nervous system lymphoma that needs attention prior to treatment of the lesions. - If the total fields of radiation will include a marrow volume of more than 40%. Physician can include as many fields to respect the 40% of marrow volume and come back in 4-6 weeks later to address the rest of the disease after insuring that the blood counts are adequate. Blood counts should be back to back to the numbers prior to starting the first phase of radiation + or - 10% variance. - If giving radiation prevents them from going through an alternative phase I trial that could be beneficial like chimeric antigen receptor (car) T cell treatment.

  • Start Date

    2019-06-14

  • Last Updated

    2019-08-09

  • Sponsor

    National Cancer Institute (NCI)

  • Condition Name

    Refractory Mantle Cell Lymphoma

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