Clinical trial NCT03042585: Autologous Transplant Using Dose-Escalated Total Body Irradiation & Cyclophosphamide & Palifermin for NHL
Official title: Phase I Study of Autologous Transplant Conditioned by Dose-Escalated Total Body Irradiation (TBI) and Standard Doses of Cyclophosphamide and Palifermin (Kepivance) for High Risk Non-Hodgkins Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Relapsed Non Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Keywords: BMT
NHL
Non-Hodgkin Lymphoma
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
autologous stem cell transplantation
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2017-02-03
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Dose-Escalated Total Body Irradiation (TBI) of 4 levels. Palifermin (Kepivance) is being supplied by the sponsor and is FDA approved to decrease the incidence and duration of severe oral mucositis in participants with hematologic malignancies who receive high doses of chemotherapy and radiation therapy followed by stem cell rescue.
Primary purpose: TREATMENT

Brief summary: Most participants with a relapsed or refractory non-Hodgkin's lymphoma that receive an autologous transplant are likely to suffer a relapse because standard myeloablative preparative regimens are unable to produce a cure. The majority of these participants do not have a stem cell donor available, are too frail to undergo an allogeneic transplant, or refuse an allograft. Historically these participants with high risk non-Hodgkin's lymphoma have had a very poor outcome.

To take advantage of the low transplant related mortality associated with an autologous transplantation, the investigators propose modifying the preparative regimen to make it more effective without increasing toxicity. By increasing the dose of radiation while administering the protective growth factor palifermin (Kepivance), the investigators hope to decrease the risk of relapse without increasing transplant related mortality.

Three prospective randomized trials have studied different radiation schemes as a part of the TBI and cytoxan preparative regimen prior to allogeneic transplantation for patients with AML or CML. As a group these trials showed that higher doses of TBI in these older studies decreased the risk of relapse at the expense of VOD, GVHD, and CMV. Three retrospective studies have also postulated that higher dose radiation led to less risk of relapse.

Detailed description: This is a non-randomized, open-label phase I trial in participants with non-Hodgkin's lymphoma. The preparative regimen will be as follows:

Day -10 (prior to transplant) Palifermin treatment to prevent mouth sores Day -9 Palifermin treatment to prevent mouth sores Day -8 Palifermin treatment to prevent mouth sores Day -7 Total Body Irradiation twice a day Day -6 Total Body Irradiation twice a day Day -5 Total Body Irradiation twice a day Day -4 Total Body Irradiation twice a day Day -3 Cytoxan chemotherapy infusion Day -2 Cytoxan chemotherapy infusion Day -1 Day of rest Day 0 Stem cell infusion (bone marrow transplant), Palifermin treatment to prevent mouth sores and G-CSF given daily until stem cells take hold (engraftment) occurs.

Day +1 Palifermin treatment to prevent mouth sores Day +2 Palifermin treatment to prevent mouth sores

Eligibility criteria: Inclusion Criteria:

* Age 18 years of age or older
* Participants scheduled to undergo autologous stem cell transplantation with relapsed or refractory non-Hodgkin's Lymphoma with less than a partial remission to salvage therapy.
* Participants scheduled to undergo autologous stem cell transplantation with relapsed or refractory non-Hodgkin's Lymphoma with any site of disease 2 cm or greater on pre-transplant imaging.
* Participants must have a performance status (PS) of 0-1.
* Participants must have acceptable kidney function.
* Acceptable pulmonary function test of the lungs.
* Acceptable liver function tests.

Exclusion Criteria:

* Participants must not have cutaneous T-cell, mantle cell, or lymphoblastic lymphoma.
* Participants must not have prior peripheral blood or marrow transplantation.
* Participants must not have prior radiation.
* Participants must not have significant history of uncontrolled cardiac disease; for example, uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
* Participants must not have active bacterial, fungal, or viral infection.

Primary outcomes:
measure: Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.
timeFrame: 4 weeks
Secondary outcomes:
measure: Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.
timeFrame: 4 weeks
measure: Pulmonary Function Test will be used to evaluate side effects of total body irradiation
timeFrame: 1 year
measure: CT scan or physical exam will be used to evaluate progression free survival.
timeFrame: 1 year
measure: Mucositis measured by investigators.
timeFrame: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
measure: Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3.
timeFrame: 28 days post treatment
measure: Mucositis measured by oral mucositis questionnaires
timeFrame: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Patrick Stiff, MD
state: Illinois
Study officials:
affiliation: Loyola University
name: Patrick Stiff, MD
role: PRINCIPAL_INVESTIGATOR
References: