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Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

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ClinicalTrials.gov Identifier: NCT00322101
Recruitment Status : Completed
First Posted : May 4, 2006
Results First Posted : October 28, 2013
Last Update Posted : October 31, 2014
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
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)
Childhood Acute Myeloid Leukemia in Remission
Childhood Myelodysplastic Syndromes
de Novo Myelodysplastic Syndromes
Myelodysplastic Syndrome With Isolated Del(5q)
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Interventions Radiation: total-body irradiation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: cyclophosphamide
Drug: mycophenolate mofetil
Drug: busulfan
Drug: cyclosporine
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Genetic: cytogenetic analysis
Other: flow cytometry
Genetic: fluorescence in situ hybridization
Other: pharmacological study
Genetic: polymorphism analysis
Drug: tacrolimus
Drug: methotrexate
Enrollment 25
Recruitment Details Patients were recruited from medical clinics while being evaluated for stem cell transplantation
Pre-assignment Details  
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Period Title: Overall Study
Started 14 11
Completed 14 11
Not Completed 0 0
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen) Total
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Total of all reporting groups
Overall Number of Baseline Participants 14 11 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 11 participants 25 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
14
 100.0%
11
 100.0%
25
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 11 participants 25 participants
51.47  (9.49) 52.82  (5.78) 52.2  (7.94)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 11 participants 25 participants
Female
8
  57.1%
3
  27.3%
11
  44.0%
Male
6
  42.9%
8
  72.7%
14
  56.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 14 participants 11 participants 25 participants
United States 8 7 15
Germany 6 4 10
1.Primary Outcome
Title Overall Survival
Hide Description [Not Specified]
Time Frame At 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
2 patients in the nonmyeloablative arm did not receive transplant due to relapse and withdrawal of consent
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
6 6
2.Secondary Outcome
Title Progression-free Survival
Hide Description IWG criteria was used to determine disease progression
Time Frame After stem cell infusion to date of last follow up.
Hide Outcome Measure Data
Hide Analysis Population Description
2 patients in the nonmyeloablative arm did not receive a transplant due to relapse and withdrawal of consent
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
7 5
3.Secondary Outcome
Title Non-relapse Mortality
Hide Description [Not Specified]
Time Frame At 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
2 patients in the nonmyeloablative arm did not receive transplant due to relapse and withdrawal of consent
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
0 0
4.Secondary Outcome
Title Donor Cell Engraftment
Hide Description Chimerism analysis was performed in patients who recieved nonmyeloablative tranplsnat. In this group the definition of engraftment was a CD3 count greater than 50%. In the myeloablative group, engraftment was defined as an absolute neutrophil count greater than 50%.
Time Frame After stem cell infusion to day 28
Hide Outcome Measure Data
Hide Analysis Population Description
2 patients who were randomized to receive nonmyeloablative conditioning did not undergo transplant due to relapse and withdrawal of consent
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
11 11
5.Secondary Outcome
Title Incidence of Disease Progression/Relapse
Hide Description Disease progression/relapse was defined by IWG criteria
Time Frame After stem cell infusion to date of last follow up.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
7 2
6.Secondary Outcome
Title Incidence and Severity of Acute and Chronic Graft-vs-host Disease
Hide Description [Not Specified]
Time Frame After transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description:

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Overall Number of Participants Analyzed 12 11
Measure Type: Number
Unit of Measure: participants
1 4
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Hide Arm/Group Description

CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.

CONDITIONING: Patients are assigned to 1 of 2 treatment groups.

Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.

Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

TRANSPLANTATION: Patients undergo PBSC infusion on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

All-Cause Mortality
Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/12 (25.00%)      4/11 (36.36%)    
Blood and lymphatic system disorders     
Thrombotic Microangiopathy  0/12 (0.00%)  0 1/11 (9.09%)  1
Cardiac disorders     
tachycardia and hypotenstion  1/12 (8.33%)  1 0/11 (0.00%)  0
Gastrointestinal disorders     
severe diarrhea due to gut GVHD  2/12 (16.67%)  2 2/11 (18.18%)  2
Mucositis  0/12 (0.00%)  0 1/11 (9.09%)  1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I (Nonmyeloablative Regimen) Arm II (Myeloablative Regimen)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/12 (100.00%)      11/11 (100.00%)    
Gastrointestinal disorders     
Mucositis  0/12 (0.00%)  0 6/11 (54.55%)  6
Infections and infestations     
Infection  12/12 (100.00%)  12 5/11 (45.45%)  5
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bart Lee Scott
Organization: Fred Hutchinson Cancer Research Center
Phone: 206-667-1990
EMail: bscott@fhcrc.org
Layout table for additonal information
Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00322101    
Other Study ID Numbers: 1992.00
NCI-2010-00737 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P01CA078902 ( U.S. NIH Grant/Contract )
K23HL084054 ( U.S. NIH Grant/Contract )
P01CA018029 ( U.S. NIH Grant/Contract )
P01HL036444 ( U.S. NIH Grant/Contract )
First Submitted: May 2, 2006
First Posted: May 4, 2006
Results First Submitted: April 4, 2013
Results First Posted: October 28, 2013
Last Update Posted: October 31, 2014