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

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Primary Purpose

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Total body irradiation

About this trial

This is an interventional treatment trial for Relapsed Non Hodgkin Lymphoma focused on measuring BMT, NHL, Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma, autologous stem cell transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Patrick Stiff, MD

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Dose Level 4

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

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.

Mucositis measured by investigators.

Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale.

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.

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.

Full Information

NCT ID

NCT03042585

First Posted

January 4, 2017

Last Updated

August 19, 2019

Sponsor

Loyola University

1. Study Identification

Unique Protocol Identification Number

NCT03042585

Brief Title

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

June 2006 (undefined)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Loyola University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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)

Allocation

Non-Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Level 1

Arm Type

Experimental

Arm 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.

Arm Title

Dose Level 2

Arm Type

Experimental

Arm 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.

Arm Title

Dose Level 3

Arm Type

Experimental

Arm 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.

Arm Title

Dose Level 4

Arm Type

Experimental

Arm 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.

Intervention Type

Radiation

Intervention Name(s)

Total body irradiation

Intervention Description

When radiation is given in a way to cover the whole body, it is called total body irradiation.

Primary Outcome Measure Information:

Title

Determine the frequency and severity of adverse events by evaluating grade 3 and grade 4 adverse events.

Description

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

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets.

Description

To evaluate labwork during treatment and for 28 days post treatment

Time Frame

4 weeks

Title

Pulmonary Function Test will be used to evaluate side effects of total body irradiation

Description

Pulmonary Function Test will be used to evaluate side effects of total body irradiation.

Time Frame

1 year

Title

CT scan or physical exam will be used to evaluate progression free survival.

Description

CT scan or physical exam will be used to evaluate progression free survival as deemed necessary.

Time Frame

1 year

Title

Mucositis measured by investigators.

Description

Mucositis physical examination done by investigators by accessing the mouth using the WHO (World Health Organization) oral toxicity scale.

Time Frame

At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.

Title

Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 3.

Description

Dose-limiting toxicities that are probably or definitely related to the treatment regimen.

Time Frame

28 days post treatment

Title

Mucositis measured by oral mucositis questionnaires

Description

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.

Time Frame

At the start of treatment and daily until mucositis resolves or 28 days post transplant whichever comes first.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrick Stiff, MD

Organizational Affiliation

Loyola University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Patrick Stiff, MD

City

Maywood

State/Province

Illinois

ZIP/Postal Code

60153

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

No

Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial