DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Accelerated Phase Chronic Myelogenous Leukemia; 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Hematopoietic/Lymphoid Cancer; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

Intervention: fludarabine phosphate (Drug); busulfan (Drug); anti-thymocyte globulin (Biological); tacrolimus (Drug); methotrexate (Drug); peripheral blood stem cell transplantation (Procedure); allogeneic hematopoietic stem cell transplantation (Procedure); laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
H. Joachim Deeg, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Summary

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

Clinical Details

Official title: Conditioning for Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Incidence of acute GvHD

Secondary outcome:

Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy

Thymoglobulin pharmacokinetics

Incidence of donor cell engraftment

Incidence of system toxicities >= grade 3 as graded per CTCAE v.3

Incidence of chronic GvHD

Incidence of non-relapse mortality defined as death without history of post-transplant relapse

Incidence of non-relapse mortality defined as death without history of post-transplant relapse

Incidence of relapse

Relapse-free survival

Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR)

Detailed description: PRIMARY OBJECTIVE: I. Determine the incidence and severity of acute graft-versus-host disease (GvHD). SECONDARY OBJECTIVES: I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy. II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics. III. Determine the incidence of donor engraftment. IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3. V. Determine the incidence and severity of chronic GvHD. VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr). VII. Determine the incidence of relapse. VIII. Determine relapse-free survival. IX. Determine the incidence of Epstein-Barr virus (EBV) activation. OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days - 9 to -6,

busulfan IV over 3 hours on days - 5 to -2, and anti-thymocyte globulin IV over 6 hours on

days - 3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem

cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally

(PO) every 12 hours beginning on day - 1 and taper to day 180 and methotrexate IV on days 1,

3, 6, and 11. After completion of study treatment, patients are followed at 1 year.

Eligibility

Minimum age: N/A. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast

phase (CP2)

- Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)

- Myelodysplastic syndromes (MDS) ( all risk groups)

- Other myeloproliferative disorders

- DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C,

DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele

- DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with

granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers

- DONOR: Age 12-75 yrs

Exclusion Criteria:

- Cardiac insufficiency requiring treatment or symptomatic coronary artery disease

- Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal

- Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion

capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted

- Impaired renal function (creatinine > 2 times normal or estimated creatinine

clearance < 60 ml/min)

- MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr)

(mg/dL)

- FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)

- Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or

acceleration of HIV replication

- Female patients who are pregnant or breast feeding

- Life expectancy severely limited by diseases other than malignancy

- DONOR: donors who for any reason are unable to tolerate the mobilization and

leukapheresis procedure

- DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive

- DONOR: female donors who have a positive pregnancy test

Locations and Contacts

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States
Additional Information

Starting date: September 2004
Last updated: November 10, 2014

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017