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Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer (Bu Flu TBI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00245037
Recruitment Status : Completed
First Posted : October 27, 2005
Results First Posted : July 2, 2017
Last Update Posted : September 27, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Precancerous Condition
Interventions: Biological: therapeutic allogeneic lymphocytes
Drug: busulfan
Drug: cyclosporine
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Radiation: Total Body Irradiation (TBI)
Drug: Granulocyte colony-stimulating factor (G-CSF)
Drug: Phenytoin
Drug: Methotrexate

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)

Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0

Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.

Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.

IV Busulfan is available and diluted and administered per package insert guidelines.

Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including


Participant Flow:   Overall Study
    Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
STARTED   147 
COMPLETED   130 [1] 
NOT COMPLETED   17 
Death                17 
[1] 17 participants died from infectious complications.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)

Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0

Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.

Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.

IV Busulfan is available and diluted and administered per package insert guidelines.

Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including


Baseline Measures
   Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) 
Overall Participants Analyzed 
[Units: Participants]
 147 
Age 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
<=18 years      0   0.0% 
Between 18 and 65 years      81  55.1% 
>=65 years      66  44.9% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
Female      49  33.3% 
Male      98  66.7% 
Karnofsky Performance Score (KPS) [1] [2] 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 139 
KPS ≥ 90      91  65.5% 
KPS < 90      48  34.5% 
[1]

KPS Scale:

100 = Normal, no complaints, no evidence of disease. 90 = Able to carry on normal activity; minor signs or symptoms of disease. 80 = Normal activity with effort; some signs or symptoms of disease. 70 = Cares for self, unable to carry on normal activity or to do active work. 60 = Requires occasional assistance, but is able to care for most of his/her needs.

50 = Requires considerable assistance and frequent medical care. 40-0 = Not eligible

[2] Eight patients did not have KPS status available, which is why the values do not add up to the total number of participants.
Pre-Transplant Disease Status 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
In Complete Remission      85  57.8% 
Not in Complete Remission      62  42.2% 
Disease Risk Index (DRI) [1] 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 144 
Low or intermediate      93  64.6% 
High or Very High      51  35.4% 
[1] DRI was unclassifiable in 3 patients.
HLA Match [1] 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
8/8      135  91.8% 
7/8      12   8.2% 
[1]

HLA Criteria:

Related to the patient and genotypically or phenotypically HLA-identical (8/8). Single antigen mismatch (7/8) can be accepted if no other donor is available.

OR

Unrelated to the patient and HLA matched by molecular typing, allowing a single allele or antigen mismatch (7/8).

Donor Relation 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
Related Sibling Donor      39  26.5% 
Unrelated Donor      108  73.5% 
Cytomegalovirus (CMV) Status [1] 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 140 
-/- recipient/donor      22  15.7% 
All other combinations      118  84.3% 
[1] Cytomegalovirus (CMV) status was unavailable in 7 patients.
Donor/Recipient Gender 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 147 
F/F, M/M, M/F      117  79.6% 
F/M      30  20.4% 


  Outcome Measures

1.  Primary:   Regimen-Related Toxicities   [ Time Frame: 5 years post-transplant ]

2.  Primary:   Non-relapse Mortality   [ Time Frame: Two years post-transplant ]

3.  Secondary:   Overall Survival   [ Time Frame: Years 1, 2, 3 and 5 ]

4.  Secondary:   Progression-Free Survival   [ Time Frame: Years 1, 2, 3, and 5 ]

5.  Secondary:   Relapse Mortality   [ Time Frame: Years 1 and 2 ]

6.  Secondary:   Acute Graft-Versus-Host Disease (aGVHD) Outcome   [ Time Frame: Day 100, Month 6 ]

7.  Secondary:   Chronic Graft-Versus-Host Disease (cGVHD) Outcome   [ Time Frame: Years 1, 2 and 3 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Richard T. Maziarz, MD
Organization: Oregon Health and Science University
phone: 503-494-6345
e-mail: maziarzr@ohsu.edu



Responsible Party: Richard Maziarz, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00245037     History of Changes
Other Study ID Numbers: IRB00000210
P30CA016058 ( U.S. NIH Grant/Contract )
OHSU-HEM-05011-L ( Other Identifier: OHSU Knight Cancer Institute )
OHSU-210 ( Other Identifier: OHSU IRB )
First Submitted: October 25, 2005
First Posted: October 27, 2005
Results First Submitted: April 20, 2017
Results First Posted: July 2, 2017
Last Update Posted: September 27, 2017