Relapsed Non Hodgkin LymphomaNCT03042585
Autologous Transplant Using Dose-Escalated Total Body Irradiation & Cyclophosphamide & Palifermin for NHL
A study testing Total body irradiation in people with Relapsed Non Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Loyola University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma
- What is being tested?
- Total body irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Total body irradiation
- Keywords
- BMT, NHL, Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, autologous stem cell transplantation
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total body irradiationRadiation
When radiation is given in a way to cover the whole body, it is called total body irradiation.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: Total body irradiation |
| 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. Receives: Radiation: Total body irradiation |
| 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. Receives: Radiation: Total body irradiation |
| 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. Receives: Radiation: Total body irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
- Hemorrhagic cystitis with frank blood requiring sclerosing agent or other surgical procedure
- Acute kidney failure requiring dialysis
- Interstitial pneumonitis requiring ventilatory support or FiO2 > 50% x 24hrs
- Bilirubin > 20 mg/dL
- Unexplained seizures or coma
- Severe mucositis requiring intubation for airway protection
- Ileus requiring nasogastric decompression.
- Death
Measured: 4 weeks
Secondary outcomes (6)
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
Measured: 4 weeks
Pulmonary Function Test will be used to evaluate side effects of total body irradiation
Pulmonary Function Test will be used to evaluate side effects of total body irradiation.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2017 (estimated)
- Study startJun 2006
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Non Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Stiff, Loyola University
- Investigators
- Patrick Stiff, MD, Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03042585
- Sponsor's protocol ID
- 108993
- Status last verified
- Aug 2019
- First submitted
- 4 Jan 2017
- Last updated
- 21 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03042585
- Acronym / sponsor ID
- 108993
- Keywords
- BMT, NHL, Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, autologous stem cell transplantation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Study start
- Jun 2006
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 3 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Radiation: Total body irradiationThe 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. |
| Dose Level 2 | Experimental | Radiation: Total body irradiationThe 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. |
| Dose Level 3 | Experimental | Radiation: Total body irradiationThe 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. |
| Dose Level 4 | Experimental | Radiation: Total body irradiationThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total body irradiationWhen radiation is given in a way to cover the whole body, it is called total body irradiation. | Radiation | Dose Level 1, Dose Level 2, Dose Level 3, Dose Level 4 |
Primary outcome
Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.
Time frame: 4 weeks
Any grade 3 or 4 dose limiting toxicities as described : • Heart failure with only minor response to medical therapy * Hemorrhagic cystitis with frank blood requiring sclerosing agent or other surgical procedure * Acute kidney failure requiring dialysis * Interstitial pneumonitis requiring ventilatory support or FiO2 > 50% x 24hrs * Bilirubin > 20 mg/dL * Unexplained seizures or coma * Severe mucositis requiring intubation for airway protection * Ileus requiring nasogastric decompression. * Death
6 secondary outcomes
Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.
Time frame: 4 weeks
Pulmonary Function Test will be used to evaluate side effects of total body irradiation
Time frame: 1 year
CT scan or physical exam will be used to evaluate progression free survival.
Time frame: 1 year
Mucositis measured by investigators.
Time frame: 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.
Time frame: 28 days post treatment
Mucositis measured by oral mucositis questionnaires
Time frame: At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Individual participant dataSharing planned: No
Related trials for Relapsed Non Hodgkin Lymphoma
Active, not recruitingObservational study
Multi-omics Profiling of Relapsed Extranodal Natural Killer (NK)/T-cell Lymphoma
Extranodal NK/T-cell Lymphoma, Nasal Type
Active, not recruitingEarly Phase 1
Iomab-ACT: A Pilot Study of 131-I Apamistamab Followed by CD19-Targeted CAR T-Cell Therapy for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia or Diffuse Large B-Cell Lymphoma
B-ALL, DLBCL
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Stiff, MD principal investigator
Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Total body irradiation in people with Relapsed Non Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Loyola University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events. (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2019.