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)

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)

This study will see if the researchers can lower that risk by giving the patient Palifermin. This drug helps protect the lining of the mouth, throat, and stomach. These areas typically get sores or ulcers while the blood cell counts are very low. The patient can get infections in or from these sores. Palifermin might also help the immune system recover faster. It is currently approved for patients who receive their own stem cells. That is called an autologous transplant. This study will test the use of Palifermin for T-cell depleted allogeneic stem cell transplants.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Advanced Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients should be < 65 years. 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 or Lansky 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 on d+1 and d+2. Supportive care will be administered as per the BMT Service; guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To Reduce the Early Transplant-related Mortality.	conclusion of study

Secondary Outcome Measures

Outcome Measure	Time Frame
To Improve the Quality of Immune Reconstitution Following Transplantation.	conclusion of study
To Reduce the Incidence Rate of Fatal Post Transplant Infectious Complications.	conclusion of study

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2008
• Primary Completion (Actual): October 20, 2020
• Study Completion (Actual): October 20, 2020

Study Registration Dates

• First Submitted: February 14, 2008
• First Submitted That Met QC Criteria: February 26, 2008
• First Posted (Estimate): March 6, 2008

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: August 27, 2021
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Melphalan; Fludarabine; Busulfan; 08-008
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Fludarabine; Busulfan; Antilymphocyte Serum
• Other Study ID Numbers: 08-008