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

NCT03042585 | Completed DMC

• 1 other identifier: 108993
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  4 weeks

Secondary Outcomes (6)

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

  4 weeks

• 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.

  1 year

• Mucositis measured by investigators.

  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.

  28 days post treatment

Study Arms (4)

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.

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.

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.

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.

Radiation: Total body irradiation

Interventions

Total body irradiation RADIATION

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

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Loyola University: lead

Study Sites (1)

Patrick Stiff, MD

Maywood, Illinois, 60153, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Patrick Stiff, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD and Director of Cardinal Bernardin Cancer Center

Model Details: 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.

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: February 3, 2017
• Study Start: June 1, 2006
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 21, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)