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

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 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Busulfan Melphalan Melphalan hydrochloride Fludarabine Fludarabine phosphate Palifermin Antilymphocyte Serum

U.S. FDA Resources

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 post transplant infectious complications. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	52
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 This is a single arm phase II trial to assess the efficacy (decrease the transplant related mortality) 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. The addition of Palifermin is to decrease the toxicity and the infection rate associated with this regimen and transplant type and to foster earlier immune reconstitution.	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 12 doses over three days of 0.8 mg/kg IV for patients > or = to 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 Other Names: Patients will receive ATG for two doses prior to transplant. G-CSF mobilized CD34+E- PBSCs (or BM if donors are unwilling or unable to donate PBSC) obtained from the HLA compatible donor will be infused on day 0. Patients will receive three additional daily doses of Palifermin, the first approximately 6 hours after the stem cell infusion on day 0, followed by two daily doses given at 24 hr intervals on d+1 and d+2. Supportive care will be administered as per the BMT Service guidelines.

Arms

Assigned Interventions

Experimental: 1

This is a single arm phase II trial to assess the efficacy (decrease the transplant related mortality) 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. The addition of Palifermin is to decrease the toxicity and the infection rate associated with this regimen and transplant type and to foster earlier immune reconstitution.

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 12 doses over three days of 0.8 mg/kg IV for patients > or = to 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

Other Names:

Patients will receive ATG for two doses prior to transplant.
G-CSF mobilized CD34+E- PBSCs (or BM if donors are unwilling or unable
to donate PBSC) obtained from the HLA compatible donor will be infused on
day 0. Patients will receive three additional daily doses of Palifermin,
the first approximately 6 hours after the stem cell infusion on day 0,
followed by two daily doses given at 24 hr intervals on d+1 and d+2.
Supportive care will be administered as per the BMT Service
guidelines.

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	212-639-8197
Contact: Farid Boulad, MD	212-639-6684

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Hugo Castro-Malaspina, MD 212-639-8197
Contact: Farid Boulad, MD 212-639-6684
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

Additional Information:

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

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00629798 History of Changes
Other Study ID Numbers:	08-008
Study First Received:	February 14, 2008
Last Updated:	June 13, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Busulfan
Melphalan
Fludarabine
08-108

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Melphalan
Fludarabine monophosphate
Fludarabine

Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on June 17, 2013