Autologous Transplant Using Dose-Escalated Total Body Irradiation & Cyclophosphamide & Palifermin for NHL
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
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.
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
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
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
-
-
Illinois
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Maywood, Illinois, Forenede Stater, 60153
- Patrick Stiff, MD
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-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Dose Level 1
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.
|
When radiation is given in a way to cover the whole body, it is called total body irradiation.
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Eksperimentel: Dose Level 2
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.
|
When radiation is given in a way to cover the whole body, it is called total body irradiation.
|
|
Eksperimentel: Dose Level 3
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.
|
When radiation is given in a way to cover the whole body, it is called total body irradiation.
|
|
Eksperimentel: Dose Level 4
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.
|
When radiation is given in a way to cover the whole body, it is called total body irradiation.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.
Tidsramme: 4 weeks
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Any grade 3 or 4 dose limiting toxicities as described : • Heart failure with only minor response to medical therapy
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4 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.
Tidsramme: 4 weeks
|
To evaluate labwork during treatment and for 28 days post treatment
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4 weeks
|
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Pulmonary Function Test will be used to evaluate side effects of total body irradiation
Tidsramme: 1 year
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Pulmonary Function Test will be used to evaluate side effects of total body irradiation.
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1 year
|
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CT scan or physical exam will be used to evaluate progression free survival.
Tidsramme: 1 year
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CT scan or physical exam will be used to evaluate progression free survival as deemed necessary.
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1 year
|
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Mucositis measured by investigators.
Tidsramme: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
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Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale.
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At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
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Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3.
Tidsramme: 28 days post treatment
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Dose-limiting toxicities that are probably or definitely related to the treatment regimen.
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28 days post treatment
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Mucositis measured by oral mucositis questionnaires
Tidsramme: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
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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.
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At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Patrick Stiff, MD, Loyola University
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 108993
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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