Autologous Transplant Using Dose-Escalated Total Body Irradiation & Cyclophosphamide & Palifermin for NHL

Loyola University

Status: Completed

Conditions: Relapsed Non Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma

Treatments: Radiation: Total body irradiation

Study type: Interventional

Funder types: Other

Identifiers

NCT03042585

108993

Details and patient eligibility

About

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.

Full 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

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 4 patient groups

Dose Level 1

Experimental group

Description:

The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.64 Gy per Fraction for a total of 8 Fractions. The total amount would be 13.12 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.

Treatment:

Radiation: Total body irradiation

Dose Level 2

Experimental group

Description:

The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.76 Gy per Fraction for a total of 8 Fractions. The total amount would be 14.08 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.

Treatment:

Radiation: Total body irradiation

Dose Level 3

Experimental group

Description:

The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 1.88 Gy per Fraction for a total of 8 Fractions. The total amount would be 15.04 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.

Treatment:

Radiation: Total body irradiation

Dose Level 4

Experimental group

Description:

The participants will receive Palifermin on Day -10, -9 and -8. Total Body Irradiation 2.00 Gy per Fraction for a total of 8 Fractions. The total amount would be 16 Gy. The participants will receive total body irradiation twice a day for four days (Day -7, -6, -5, and Day -4). Over the following two days, the participants will receive cyclophosphamide (Day -3 and -2). The participants will receive stem cell infusion on Day 0 and G-CSF given daily until engraftment occurs. Participants will receive Palifermin on Day 0, +1 and +2.

Treatment:

Radiation: Total body irradiation