Busulfan, Melphalan, and Fludarabine With Peri-Transplant Palifermin, Followed by a T-Cell Depleted Hematopoietic Stem Cell Transplant From HLA Matched or Mismatched Related or Unrelated Donors in Patients With Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) - Full Text View

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00629798

Purpose

The purpose of this study is to find out how good the addition of Palifermin to the conditioning regimen for a T cell depleted allogeneic stem cell transplant is at lowering the fatal infectious complications associated with the transplant. The conditioning regimen is the treatment given before transplantation and will include busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG). An earlier study at this institution showed that the same conditioning regimen without Palifermin and the same type of transplant was safe and able to cure patients with MDS/AML. However, the success rate was lowered by fatal infectious complications happening after the transplant. The new part of this study is the addition of Palifermin before and after administration of the pre-transplant treatments to lower these complications. The purpose of this study is also to find out the possible bad side effects of this new regimen.

Condition	Intervention	Phase
Acute Myeloid Leukemia Advanced Myelodysplastic Syndromes	Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Melphalan Fludarabine Fludarabine monophosphate Granulocyte colony-stimulating factor Melphalan hydrochloride Sarcolysin Busulfan Palifermin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Trial of Busulfan, Melphalan, and Fludarabine With Peri-Transplant Palifermin, Followed by a T-Cell Depleted Hematopoietic Stem Cell Transplant From HLA Matched or Mismatched Related or Unrelated Donors in Patients With Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To reduce the early transplant-related mortality. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To improve the quality of immune reconstitution following transplantation. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]
To reduce the incidence rate of fatal posttransplant infectious complications. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2011
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental This is a single arm phase II trial to assess the efficacy (decrease the transplant-related morbidity) and safety of peri-transplant Palifermin in combination with a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor in patients with advanced MDS and AML evolved from MDS.	Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant Patients will receive Palifermin 60 mcg/kg/day IV on three consecutive days with the last dose administered no less than 24 and no more than 48 hr prior to start of cytoreduction. The preparative regimen to be used for transplants will consist: of busulfan administered in 10 doses over three days of 0.8 mg/kg IV for patients > 4 years of age or 1.0 mg/kg IV for patients < 4 years of age; melphalan 70 mg/m2 IV x 2 days; and, fludarabine 25 mg/m2 IV x 5 days

Arms

Assigned Interventions

1: Experimental

This is a single arm phase II trial to assess the efficacy (decrease the transplant-related morbidity) and safety of peri-transplant Palifermin in combination with a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor in patients with advanced MDS and AML evolved from MDS.

Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant

Patients will receive Palifermin 60 mcg/kg/day IV on three consecutive days with the last dose administered no less than 24 and no more than 48 hr prior to start of cytoreduction. The preparative regimen to be used for transplants will consist: of busulfan administered in 10 doses over three days of 0.8 mg/kg IV for patients > 4 years of age or 1.0 mg/kg IV for patients < 4 years of age; melphalan 70 mg/m2 IV x 2 days; and, fludarabine 25 mg/m2 IV x 5 days

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients should be < 65 years. There is no lower age limit. Patients > or equal to 65 years will be accrued on a case by case basis after discussion and approval by the BMT Service.
Patients may be of either gender or any ethnic background.
Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or equal to 70%.
Patients must have adequate organ function measured by:

* Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or equal to 50% and must improve with exercise.
Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
- Renal: serum creatinine < than or equal to 1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
Each patient must be willing to participate as a research subject and must sign an informed consent form.
Parent or legal guardians of patients who are minors will sign the informed consent form.

Exclusion Criteria:

Active CNS or skin leukemic involvement
Female patients who are pregnant or breast-feeding
Active viral, bacterial or fungal infection
Patient seropositive for HIV-I/II; HTLV -I/II
Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months.
Patients who have had a previous malignancy that is not in remission.
Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving PBSC or bovine proteins if receiving SBA-E- bone marrow, or chicken egg products.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00629798

Contacts

Contact: Hugo Castro-Malaspina, MD		castro-h@mskcc.org
Contact: Farid Boulad, MD		bouladf@mskcc.org

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Hugo Castro-Malaspina, MD castro-h@mskcc.org
Contact: Farid Boulad, MD bouladf@mskcc.org
Principal Investigator: Hugo Castro-Malaspina, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Hugo Castro-Malaspina, MD

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Hugo Castro-Malaspina, M.D. )
Study ID Numbers:	08-008
Study First Received:	February 14, 2008
Last Updated:	October 1, 2008
ClinicalTrials.gov Identifier:	NCT00629798
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Myelodysplastic syndromes
Melphalan
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Acute myelogenous leukemia
Leukemia, Myeloid
Fludarabine monophosphate

Leukemia, Myeloid, Acute
Antilymphocyte Serum
Leukemia
Preleukemia
Busulfan
Fludarabine
Bone Marrow Diseases
Acute myelocytic leukemia

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009