Efficacy Study of T Cell Depleted Allogeneic Non-Myeloablative Stem Cell Transplant - Full Text View

Sponsored by:	Duke University
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00597714

Purpose

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.

Condition	Intervention	Phase
Hodgkin's Disease Non Hodgkin's Lymphoma Myeloma Leukemia Myelodysplasia	Procedure: Non-myeloablative Stem Cell Transplantation	Phase II

MedlinePlus related topics: Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Melphalan Fludarabine Fludarabine monophosphate Granulocyte colony-stimulating factor Alemtuzumab Melphalan hydrochloride Sarcolysin Campath Busulfan Diphenhydramine Diphenhydramine citrate Diphenhydramine hydrochloride Promethazine Promethazine hydrochloride Acetaminophen

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	Efficacy Study of T Cell Depleted Allogeneic Non-Myeloablative Stem Cell Transplantation

Further study details as provided by Duke University:

Primary Outcome Measures:

Estimate toxicity, disease free, progression free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate immune recovery following this reduced intensity allogeneic immunotherapy. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Develop an in vitro assay to allow patient individualized targeted dosing for busulfan [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	189
Study Start Date:	February 2008
Estimated Study Completion Date:	January 2017
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Cohorts A and B: Experimental Group A: Patients with a high chance of progressive lymphoid or myelomatous disease. Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.	Procedure: Non-myeloablative Stem Cell Transplantation Donor will receive G-CSF 8 mcg/kg/d subcutaneously bid for 4 days, until pheresis is completed or until WBC is > 100,000. Recipients in both cohorts will be premedicated with Benadryl 50 mg IV or PO, and acetaminophen 650 mg orally (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. For the Group B cohort, the prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The PBSCs will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Arms

Assigned Interventions

Cohorts A and B: Experimental

Group A: Patients with a high chance of progressive lymphoid or myelomatous disease.

Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Procedure: Non-myeloablative Stem Cell Transplantation

Donor will receive G-CSF 8 mcg/kg/d subcutaneously bid for 4 days, until pheresis is completed or until WBC is > 100,000. Recipients in both cohorts will be premedicated with Benadryl 50 mg IV or PO, and acetaminophen 650 mg orally (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. For the Group B cohort, the prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The PBSCs will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Detailed Description:

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have CALGB PS 0, 1, or 2; must have a 3-6/6 HLA-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide PBPCs and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have their diagnosis confirmed at the transplant center.
Performance status must be CALGB PS 0, 1, or 2.
Patients must have a 3-6/6 HLA-matched related donor or 8/8 or better allele level match MUD matched unrelated donor (at A,B, C, DRB1, DQ).
HIV negative.
Women of child bearing potential must have a negative pregnancy serum beta-HCG test within 1 week of starting therapy.
Patients > or equal to 18 years of age are eligible.
Patients must have a MUGA and/or ECHO or cardiac MR and PFTs with DLCO performed before transplant.
Specific patient populations:
- Group A) Patients with a high chance of progressive lymphoid or myelomatous diseases.
- Group B) Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders

Exclusion Criteria:

Pregnant or lactating women.
Patients with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
Patients with uncontrolled, progressive infections.
Patients who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
Patients with active CNS disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597714

Contacts

Contact: Jennifer Loftis, RN, BSN, OCN	919-668-1939	lofti002@mc.duke.edu
Contact: Donna Adams, RN, BSN, OCN	919-668-4716	adams068@mc.duke.edu

Locations

United States, North Carolina
Duke University Health System	Recruiting
Durham, North Carolina, United States, 27710
Contact: David Rizzieri, MD 919-668-1014 rizzi003@mc.duke.edu
Contact: Nelson Chao, MD 919-668-1011 chao0002@mc.duke.edu
Principal Investigator: David Rizzieri, MD

Sponsors and Collaborators

Duke University

Investigators

Principal Investigator:

David Rizzieri, MD

Duke University Health System

More Information

Responsible Party:	Duke University Health System, Department of Medicine, Cell Therapy Div. ( David Rizzieri, MD )
Study ID Numbers:	00003567
Study First Received:	January 14, 2008
Last Updated:	September 18, 2008
ClinicalTrials.gov Identifier:	NCT00597714
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

Stem Cell Transplantation, Non-myeloablative

Study placed in the following topic categories:

Neural Tube Defects
Melphalan
Hydrocortisone
Hodgkin's disease
Precancerous Conditions
Nervous System Malformations
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Leukemia
Preleukemia
Promethazine
Multiple myeloma
Alemtuzumab
Congenital Abnormalities
Hodgkin Disease

Lymphoma
Acetaminophen
Myelodysplastic syndromes
Immunoproliferative Disorders
Cortisol succinate
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Fludarabine monophosphate
Multiple Myeloma
Lymphatic Diseases
Busulfan
Neural tube defect, folate-sensitive
Fludarabine
Hydrocortisone acetate

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on January 16, 2009