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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Level 1 | Experimental | 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. |
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| Dose Level 2 | Experimental | 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. |
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| Dose Level 3 | Experimental | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Total body irradiation | Radiation | When radiation is given in a way to cover the whole body, it is called total body irradiation. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events. | Any grade 3 or 4 dose limiting toxicities as described : • Heart failure with only minor response to medical therapy
| 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets. | To evaluate labwork during treatment and for 28 days post treatment | 4 weeks |
| Pulmonary Function Test will be used to evaluate side effects of total body irradiation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Stiff, MD | Loyola University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Patrick Stiff, MD | Maywood | Illinois | 60153 | United States |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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| ID | Term |
|---|---|
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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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.
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| Dose Level 4 | Experimental | 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. |
|
Pulmonary Function Test will be used to evaluate side effects of total body irradiation. |
| 1 year |
| CT scan or physical exam will be used to evaluate progression free survival. | CT scan or physical exam will be used to evaluate progression free survival as deemed necessary. | 1 year |
| Mucositis measured by investigators. | Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale. | At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first. |
| Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3. | Dose-limiting toxicities that are probably or definitely related to the treatment regimen. | 28 days post treatment |
| Mucositis measured by oral mucositis questionnaires | The participants will complete the oral mucositis daily questionnaires prior to the physical assessment. The questionnaire includes the participants self-reported mouth and throat soreness. | At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first. |
| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |