Clinical trial NCT00809276: Allo BMT Using Matched Related/Unrelated Donors With FluBu and HiCY
Official title: Trial of Allogeneic BMT for Hematologic Malignancies Using HLA-matched Related or Unrelated Donors With Fludarabine and IV Busulfan as Pre-transplant Conditioning Followed by Post-transplant Immunosuppression With High-dose Cyclophosphamide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Multiple Myeloma
Leukemia
Myelodysplastic Syndrome
Keywords: Acute lymphocytic leukemia (ALL)
Acute myeloid leukemia (AML)
Acute Leukemia
Refractory or Relapsed AML
Myelodysplastic syndrome (MDS)
Chronic myeloid leukemia (CML)
Chronic myelomonocytic leukemia
Hodgkin's Lymphoma
Non-Hodgkin's lymphoma
Philadelphia-negative myeloproliferative disorder
Hematologic Malignancies
Transplantation
Busulfan
Fludarabine
Cytoxan
Bone Marrow
Allogeneic
Related donor
unrelated donor
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: M.D. Anderson Cancer Center
name: Fred Hutchinson Cancer Center
name: Otsuka Pharmaceutical Co., Ltd.
First posted: 2008-12-17
Enrollment: 92
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research is to find the most effective and least toxic way to prevent GVHD after BMT.

Detailed description: A person who has cancer of the blood or lymph glands can be treated by bone marrow transplantation (BMT). BMT has developed over several decades of research on both animal and human subjects as an effective treatment of various malignant and nonmalignant hematologic diseases. Many hematologic malignancies can be successfully treated with a combination of high-dose chemotherapy or chemo-radiotherapy and transplantation of allogeneic bone marrow or peripheral blood stem cells (alloBMT)

However, a possible side effect of BMT is graft versus host disease (GVHD). GVHD occurs when cells of the donor's immune system, which are present in the bone marrow, attack the BMT recipient's normal tissue. Prevention of GVHD is important for the success of the bone marrow transplant. This research is being done to find the most effective and least toxic way to prevent GVHD after BMT

Eligibility criteria: Inclusion Criteria:

* Patients ages between 0 to and 65 years of age.
* Patient must have a genotypically HLA-identical sibling, a phenotypically matched first-degree relative or an unrelated matched donor.
* Acute lymphocytic leukemia (ALL) in CR1 with high risk features
* Acute myeloid leukemia (AML) in CR1 with high risk features defined as:

  i. Greater than 1 cycle of induction therapy required to achieve remission, ii. Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML iii. Presence of Flt3 mutations or internal tandem duplications, iv. FAB M6 or M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia, or v. Complex karyotype \[\> 3 abnormalities\]
* Acute Leukemias in 2nd or greater remission
* Refractory or Relapsed AML
* AML transformed from MDS
* Myelodysplastic syndrome (MDS) beyond refractory anemia
* Chronic myeloid leukemia (CML)
* Chronic myelomonocytic leukemia
* Philadelphia-negative myeloproliferative disorder
* Relapsed chemotherapy-sensitive Hodgkin's or Non-Hodgkin's lymphoma
* Multiple Myeloma-Stage III

Exclusion Criteria:

* Prior autologous or allogeneic stem cell transplant.
* Performance status greater than 2
* Active infection.
* Inadequate cardiac function; arrythmias or symptomatic cardiac disease.
* Inadequate pulmonary function; FEV1, FVC, DLCO \<50% of predicted
* Inadequate Serum creatinine clearance \<60
* InadequatebHepatic function
* Positive serology for HIV-1, 2 or HTLV-1, 2.
* Pregnancy. Female patient must have negative pregnancy test

Primary outcomes:
measure: To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Sydney Kimmel Comprehensive Cancer center
state: Maryland
city: Houston
country: United States
facility: Marcos deLima, MD
state: Texas
city: Seattle
country: United States
facility: Paul V. O'Donnell, M.D., Ph.D.
state: Washington
Study officials:
affiliation: Johns Hopkins University
name: Leo Luznik, MD
role: STUDY_CHAIR
References:
citation: Kanakry CG, O'Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, Mielcarek M, Champlin RE, Jones RJ, Thall PF, Andersson BS, Luznik L. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014 Nov 1;32(31):3497-505. doi: 10.1200/JCO.2013.54.0625. Epub 2014 Sep 29.