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Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy

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ClinicalTrials.gov Identifier: NCT00796562
Recruitment Status : Completed
First Posted : November 24, 2008
Results First Posted : March 14, 2019
Last Update Posted : March 14, 2019
Sponsor:
Collaborators:
Otsuka Pharmaceutical Co., Ltd.
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions MDS
Leukemias
Lymphomas
Interventions Drug: Busulfan
Drug: Cyclophosphamide
Radiation: Total body irradiation
Enrollment 107
Recruitment Details  
Pre-assignment Details 11 participants were screen failures.
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Period Title: Overall Study
Started 96
Completed 47
Not Completed 49
Reason Not Completed
Death             49
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Baseline Participants 96
Hide Baseline Analysis Population Description
The entire set of participants was analyzed as one group, and the analysis was planned this way from the beginning of the study.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
<=18 years
15
  15.6%
Between 18 and 65 years
80
  83.3%
>=65 years
1
   1.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 96 participants
42
(1 to 65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 96 participants
Female
40
  41.7%
Male
56
  58.3%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 96 participants
96
 100.0%
1.Primary Outcome
Title Engraftment as Measured by Donor Chimerism
Hide Description Percentage of participants who achieved donor chimerism >=95%.
Time Frame Day 60
Hide Outcome Measure Data
Hide Analysis Population Description
8 participants were not evaluable for this outcome because they died prior to Day 60.
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
91
(83 to 96)
2.Secondary Outcome
Title Non-relapse Mortality
Hide Description Number of participants deceased for reasons other than disease relapse or progression.
Time Frame Day 100, 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 96
Measure Type: Count of Participants
Unit of Measure: Participants
100 days
10
  10.4%
1 year
10
  10.4%
3.Secondary Outcome
Title Acute GVHD
Hide Description

Percentage of participants who experience grade II-IV or III-IV acute graft-versus-host-disease (GVHD) by Przepiorka criteria. The stages are defined as follows:

  • Stage II: Rash on >50% of skin, bilirubin 2-3 mg/dL, or diarrhea 500-1000 mL/day
  • Stage III: Bilirubin 3-15 mg/dL or diarrhea >1000 mL/day
  • Stage IV: Generalized erythroderma with bullae or bilirubin >15 mg/dL This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Grade II-IV
11
(5 to 18)
Grade III-IV
4
(0 to 8)
4.Secondary Outcome
Title Chronic GVHD
Hide Description Percentage of participants who experience chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
Time Frame 6 months, 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6 months
4
(0 to 8)
12 months
15
(8 to 22)
5.Secondary Outcome
Title Survival
Hide Description Percentage of participants alive (overall survival) and alive without disease relapse, progression, or diagnosis of myeloid malignancy (event-free survival). Estimated using Kaplan-Meier method.
Time Frame 1 year, 2 years, 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Overall survival, 1 year
73
(65 to 82)
Overall survival, 2 years
57
(48 to 68)
Overall survival, 3 years
54
(44 to 65)
Event-free survival, 1 year
58
(48 to 69)
Event-free survival, 2 years
52
(42 to 63)
Event-free survival, 3 years
50
(41 to 62)
6.Secondary Outcome
Title Relapse
Hide Description Percentage of participants who experienced disease progression or relapse. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)
Time Frame 1 year, 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
The entire set of participants was analyzed as one group, and the analysis was planned this way from the beginning of the study.
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description:
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
Overall Number of Participants Analyzed 96
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1 year
35
(26 to 45)
3 years
43
(33 to 553)
Time Frame Up to 2 years
Adverse Event Reporting Description Only the following adverse events were collected per protocol: non-relapse mortality in the first 100 days after BMT; graft failure; and all unexpected events considered significant by the principal investigator. Adverse events were assessed weekly through Day 60 and at Days 180, 365, and 730.
 
Arm/Group Title Myeloablative Haploidentical BMT
Hide Arm/Group Description
  • All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
  • Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.
All-Cause Mortality
Myeloablative Haploidentical BMT
Affected / at Risk (%)
Total   49/96 (51.04%)    
Show Serious Adverse Events Hide Serious Adverse Events
Myeloablative Haploidentical BMT
Affected / at Risk (%) # Events
Total   22/96 (22.92%)    
Blood and lymphatic system disorders   
Deep vein thrombosis  1  1/96 (1.04%)  1
Cardiac disorders   
Cardiac arrest  1  1/96 (1.04%)  1
Cardiomegaly  1  1/96 (1.04%)  1
Cardiomyopathy  1  1/96 (1.04%)  1
Hypotension  1  1/96 (1.04%)  1
Pericardial effusion  1  1/96 (1.04%)  1
Sinus tachycardia  1  1/96 (1.04%)  1
Superior vena cava syndrome  1  1/96 (1.04%)  1
General disorders   
Bleeding  1  1/96 (1.04%)  1
Hepatobiliary disorders   
Liver failure  1  2/96 (2.08%)  2
Veno-occlusive disease  1  3/96 (3.13%)  5
Immune system disorders   
Liver graft-versus-host-disease  1  1/96 (1.04%)  1
Hemolytic anemia  1  1/96 (1.04%)  1
Multisystem organ dysfunction syndrome  1  3/96 (3.13%)  3
Infections and infestations   
Aspergillosis  1  1/96 (1.04%)  1
BK virus  1  2/96 (2.08%)  2
Cytomegalovirus  1  1/96 (1.04%)  1
Coagulase-negative staphylococcus  1  1/96 (1.04%)  1
Coronavirus NL63  1  1/96 (1.04%)  1
Multi-drug resistant Klebsiella bacteremia  1  1/96 (1.04%)  1
Fungal pneumonia  1  3/96 (3.13%)  3
Fungal sinusitis  1  1/96 (1.04%)  1
Human herpesvirus 6  1  1/96 (1.04%)  1
Human metapneumovirus  1  1/96 (1.04%)  1
Febrile neutropenia  1  1/96 (1.04%)  1
Pneumonia  1  1/96 (1.04%)  1
Rhinovirus  1  1/96 (1.04%)  1
Sepsis  1  3/96 (3.13%)  3
Vancomycin-resistant Enterococcus  1  1/96 (1.04%)  1
Investigations   
Graft failure  1  2/96 (2.08%)  2
Metabolism and nutrition disorders   
Metabolic acidosis  1  2/96 (2.08%)  2
Respiratory and metabolic acidosis  1  1/96 (1.04%)  1
Musculoskeletal and connective tissue disorders   
Fracture  1  1/96 (1.04%)  1
Nervous system disorders   
Altered mental status  1  1/96 (1.04%)  1
Intracranial hemorrhage  1  1/96 (1.04%)  1
Posterior reversible encephalopathy syndrome  1  1/96 (1.04%)  1
Subarachnoid hemorrhage  1  1/96 (1.04%)  1
Renal and urinary disorders   
Renal failure  1  9/96 (9.38%)  10
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  2/96 (2.08%)  2
Respiratory failure  1  6/96 (6.25%)  6
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Myeloablative Haploidentical BMT
Affected / at Risk (%) # Events
Total   37/96 (38.54%)    
Infections and infestations   
BK virus  1  6/96 (6.25%)  6
Clostridium difficile  1  13/96 (13.54%)  13
Cytomegalovirus  1  14/96 (14.58%)  19
Febrile neutropenia  1  7/96 (7.29%)  7
Renal and urinary disorders   
Acute kidney injury  1  8/96 (8.33%)  8
Skin and subcutaneous tissue disorders   
Mucositis  1  10/96 (10.42%)  10
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
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: Heather Symons, MD
Organization: Johns Hopkins University
Phone: 4105029961
EMail: hsymons2@jhmi.edu
Publications:
Fine J.P. and Gray, R.J. (1999), A proportional hazards model for the subdistribution of a competing risk, Journal of the American Statistical Association, 94:496-509.
Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00796562     History of Changes
Other Study ID Numbers: J0820
NA_00015795 ( Other Identifier: JHMIRB )
KL2RR025006 ( U.S. NIH Grant/Contract )
First Submitted: November 20, 2008
First Posted: November 24, 2008
Results First Submitted: February 12, 2019
Results First Posted: March 14, 2019
Last Update Posted: March 14, 2019