Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer

• Sponsor: Martin, Paul (Other)
• Overall Status: Completed
• CT.gov ID: NCT01233921
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Location: 1
• Arms: 2

Study Details

Study Description

Brief Summary

RATIONALE: Growth factors, such as palifermin, may prevent chronic graft-versus-host disease caused by donor stem cell transplant.

PURPOSE: This randomized clinical trial studies palifermin in preventing chronic graft-versus-host disease in patients who have undergone donor stem cell transplant for hematologic cancer

Condition or Disease	Intervention/Treatment	Phase
Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma	Biological: palifermin; Other: flow cytometry; Other: laboratory biomarker analysis; Other: pharmacological study	N/A

Detailed Description

OBJECTIVES:

1. To evaluate the pharmacodynamic effects of palifermin on thymic function in patients at risk of chronic graft-vs-host disease (GVHD).

2. To evaluate the tolerability of palifermin in patients at risk of chronic GVHD.

OUTLINE: Patients are assigned to 1 of 2 groups based on whether they wish to receive palifermin or not.

GROUP 1: Patients receive palifermin intravenously (IV) on days 1-3 in the absence of unacceptable toxicity.

GROUP 2: Patients do not receive palifermin.

After completion of study treatment, patients are followed up on days 7, 14, 21, and 28.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Preliminary Study to Evaluate the Effects of Palifermin in Patients at Risk of Chronic Graft-versus-host Disease
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (palifermin) Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.	Biological: palifermin; Given IV; Other Names: growth factor, recombinant human keratinocyte Kepivance keratinocyte growth factor, recombinant human recombinant human keratinocyte growth factor rhKGF ; Other: flow cytometry; Correlative studies; Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies
Active Comparator: Arm II (no palifermin) Patients do not receive palifermin.	Other: flow cytometry; Correlative studies; Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

Outcome Measures

Primary Outcome Measures

1. Changes in the Number of Recent Thymic Emigrants (RTE) Cluster of Differentiation (CD)4 T Cells in the Blood [Baseline and 4 weeks after administration of palifermin]

   RTE CD4 T cells will be defined according to co-expression of CD3, CD4, CD31, CD45RA, and CCR7. Cells will be counted by flow cytometry at baseline and at 4 weeks and changes will be measured as cells per microliter of blood. Positive results indicate an increase in the number of cells between baseline and 4 weeks. Negative results indicate a decrease in the number of cells between baseline and 4 weeks.

Secondary Outcome Measures

1. Changes in the Number of Naive CD4 T Cells in the Blood [Baseline and 4 weeks after administration of palifermin]

   Naive CD4 T cells will be defined according to co-expression of CD3, CD4, CD45RA, and CCR7. Positive results indicate an increase in the number of cells between baseline and 4 weeks. Negative results indicate a decrease in the number of cells between baseline and 4 weeks.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Survival for more than 60 days after an allogeneic hematopoietic cell transplantation (HCT) with growth-factor mobilized blood cells

• Current dose of prednisone at =< 0.5 mg/kg or equivalent or no systemic glucocorticoid treatment

• Ability to remain under care at the Seattle Cancer Care Alliance (SCCA) for at least 28 days after enrollment in the study

• Able and willing to give informed consent

Exclusion Criteria:

• Presence of generalized rash involving more than 50% of the body surface

• Prior diagnosis of chronic GVHD requiring systemic immunosuppressive treatment

• Any prior local irradiation to a field that included the thymus (total body irradiation is allowed)

• History of thymectomy

• Use of rabbit antithymocyte globulin in the pretransplant conditioning regimen

• Use of a graft depleted of T cells

• Any evidence of recurrent or persistent malignancy after HCT

• Participation in another study with chronic GVHD as the primary endpoint

• Any prior history of carcinoma

• Any infection that is not improving during appropriate treatment

• History of palifermin intolerance

• A positive pregnancy test (women of child-bearing potential)

• Breast feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Martin, Paul
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Martin, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martin, Paul, Member, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
• ClinicalTrials.gov Identifier: NCT01233921
• Other Study ID Numbers: 2437.00; NCI-2010-01711
• First Posted: Nov 3, 2010
• Last Update Posted: Apr 2, 2014
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Preleukemia; Lymphoma, Non-Hodgkin; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Hypereosinophilic Syndrome; Leukemia, Neutrophilic, Chronic; Graft vs Host Disease; Syndrome; Recurrence; Mitogens

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled between Nov 2010 and June 2012 during outpatient follow-up after allogeneic hematopoietic cell tranpslantation.

Arm/Group Title	Arm I (Palifermin)	Arm II (no Palifermin)
Arm/Group Description	Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.	Patients do not receive palifermin.
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Palifermin)	Arm II (no Palifermin)	Total
Arm/Group Description	Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.	Patients do not receive palifermin.	Total of all reporting groups
Overall Participants	3	3	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	3 100%	6 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44 (13)	41 (11)	43 (11)
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 16.7%
Male	2 66.7%	3 100%	5 83.3%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Changes in the Number of Recent Thymic Emigrants (RTE) Cluster of Differentiation (CD)4 T Cells in the Blood
Description	RTE CD4 T cells will be defined according to co-expression of CD3, CD4, CD31, CD45RA, and CCR7. Cells will be counted by flow cytometry at baseline and at 4 weeks and changes will be measured as cells per microliter of blood. Positive results indicate an increase in the number of cells between baseline and 4 weeks. Negative results indicate a decrease in the number of cells between baseline and 4 weeks.
Time Frame	Baseline and 4 weeks after administration of palifermin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Palifermin)	Arm II (no Palifermin)
Arm/Group Description	Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.	Patients do not receive palifermin.
Measure Participants	3	3
Mean (Standard Deviation) [cells per microliter of blood]	-2 (3)	-22 (51)

2. Secondary Outcome

Title	Changes in the Number of Naive CD4 T Cells in the Blood
Description	Naive CD4 T cells will be defined according to co-expression of CD3, CD4, CD45RA, and CCR7. Positive results indicate an increase in the number of cells between baseline and 4 weeks. Negative results indicate a decrease in the number of cells between baseline and 4 weeks.
Time Frame	Baseline and 4 weeks after administration of palifermin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Palifermin)	Arm II (no Palifermin)
Arm/Group Description	Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.	Patients do not receive palifermin.
Measure Participants	3	3
Mean (Standard Deviation) [cells per microliter of blood]	-3 (4)	-25 (58)

Adverse Events

Arm/Group Title	Arm I (Palifermin)		Arm II (no Palifermin)
Arm/Group Description	Patients receive palifermin IV on days 1-3 in the absence of unacceptable toxicity.		Patients do not receive palifermin.
All Cause Mortality
	Arm I (Palifermin)		Arm II (no Palifermin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Palifermin)		Arm II (no Palifermin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Palifermin)		Arm II (no Palifermin)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		2/3 (66.7%)
Gastrointestinal disorders
oral mucosal change	3/3 (100%)		0/3 (0%)
anorexia	2/3 (66.7%)		0/3 (0%)
nausea	2/3 (66.7%)		0/3 (0%)
vomiting	1/3 (33.3%)		0/3 (0%)
diarrhea	3/3 (100%)		1/3 (33.3%)
General disorders
edema	1/3 (33.3%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
pain	2/3 (66.7%)		1/3 (33.3%)
arthralgia	2/3 (66.7%)		0/3 (0%)
Skin and subcutaneous tissue disorders
rash	2/3 (66.7%)		1/3 (33.3%)
pruritis	0/3 (0%)		1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.