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Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

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ClinicalTrials.gov Identifier: NCT00856388
Recruitment Status : Active, not recruiting
First Posted : March 5, 2009
Results First Posted : June 13, 2016
Last Update Posted : December 5, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Accelerated Phase Chronic Myelogenous Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Lymphoblastic Leukemia in Remission
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)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Aplastic Anemia
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Fanconi Anemia
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Paroxysmal Nocturnal Hemoglobinuria
Previously Treated Myelodysplastic Syndromes
Primary Myelofibrosis
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Splenic Marginal Zone Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Waldenström Macroglobulinemia
Interventions Drug: fludarabine phosphate
Drug: melphalan
Radiation: total-body irradiation
Procedure: allogeneic hematopoietic stem cell transplantation
Biological: anti-thymocyte globulin
Enrollment 62
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Period Title: Overall Study
Started 62
Completed 61
Not Completed 1
Reason Not Completed
Not Specified             1
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Baseline Participants 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants
<=18 years
2
   3.2%
Between 18 and 65 years
43
  69.4%
>=65 years
17
  27.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 62 participants
54.6  (14.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants
Female
29
  46.8%
Male
33
  53.2%
1.Primary Outcome
Title Day 100 TRM
Hide Description Day 100 Treatment Related Mortality An exact 95% confidence interval will be provided.
Time Frame First 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.44
(3.08 to 17.29)
2.Secondary Outcome
Title Median Time to ANC Engraftment
Hide Description

Median Time to ANC Engraftment

Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

Time Frame Days 30
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 61
Median (Full Range)
Unit of Measure: Days
16.5
(0 to 26)
3.Secondary Outcome
Title Median Time to Platelet Engraftment
Hide Description

Median Time to Platelet Engraftment

Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 61
Median (Full Range)
Unit of Measure: Days
17.0
(0 to 74)
4.Secondary Outcome
Title Rate of Complete Donor Chimerism - Blood
Hide Description

Rate of Complete Donor Chimerism - Blood

Summarized using standard descriptive statistics.

Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients, who were able to complete testing
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 44
Measure Type: Number
Unit of Measure: percentage of participants
89
5.Secondary Outcome
Title Rate of Complete Donor Chimerism - Blood
Hide Description

Rate of Complete Donor Chimerism - Blood

Summarized using standard descriptive statistics.

Time Frame Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients, who were able to complete testing
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 49
Measure Type: Number
Unit of Measure: percentage of participants
94
6.Secondary Outcome
Title Acute GVHD Grade III-IV
Hide Description

Acute GVHD grade III-IV

Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

Time Frame Up to day 100
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
27
(16 to 38)
7.Secondary Outcome
Title 1 yr Extenstive Chronic GVHD
Hide Description

1 yr Extensive Chronic GVHD

Summarized using standard descriptive statistics along with corresponding 95% confidence intervals.

Time Frame Up to 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible who survived to day 100 and were eligible to get chronic GVHD
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

Overall Number of Participants Analyzed 53
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
60
(45 to 73)
8.Secondary Outcome
Title 3 yr Overall Survival
Hide Description 3 yr Overall Survival estimated using the Kaplan-Meier method.
Time Frame Up to 4.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description:

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo total-body irradiation

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic stem cell transplantation

anti-thymocyte globulin: Given IV

Overall Number of Participants Analyzed 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.0
(33.0 to 57.0)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Hide Arm/Group Description

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan* IV over 30 minutes on day -2. Patients then undergo total-body irradiation on day -1 and allogeneic stem cell transplantation on day 0.

Note: *Patients with chromosomal breakage syndromes, such as Fanconi anemia or dyskeratosis congenita, receive anti-thymocyte globulin IV over 4 hours on day -4 to -2 instead of melphalan.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo total-body irradiation

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic stem cell transplantation

anti-thymocyte globulin: Given IV

All-Cause Mortality
Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Affected / at Risk (%) # Events
Total   34/62 (54.84%)    
Blood and lymphatic system disorders   
Febrile neutropenia   1/62 (1.61%)  1
Cardiac disorders   
Atrial tachycardia   1/62 (1.61%)  1
Cardiac disorder   2/62 (3.23%)  3
Cardio-respiratory arrest   1/62 (1.61%)  1
Gastrointestinal disorders   
Abdominal pain   1/62 (1.61%)  1
General disorders   
Death   5/62 (8.06%)  5
Disease progression   1/62 (1.61%)  1
Multi-organ failure   1/62 (1.61%)  1
Pain   1/62 (1.61%)  1
Pyrexia   5/62 (8.06%)  6
Immune system disorders   
Graft versus host disease   8/62 (12.90%)  9
Infections and infestations   
Bacteraemia   2/62 (3.23%)  2
Cellulitis   1/62 (1.61%)  1
Infection   2/62 (3.23%)  2
Metabolism and nutrition disorders   
Dehydration   1/62 (1.61%)  1
Nervous system disorders   
Cerebral haemorrhage   1/62 (1.61%)  1
Headache   1/62 (1.61%)  1
Renal and urinary disorders   
Anuria   1/62 (1.61%)  1
Haematuria   2/62 (3.23%)  3
Renal failure   2/62 (3.23%)  3
Urinary tract disorder   1/62 (1.61%)  1
Respiratory, thoracic and mediastinal disorders   
Lung disorder   2/62 (3.23%)  2
Pneumonitis   1/62 (1.61%)  1
Respiratory distress   1/62 (1.61%)  1
Respiratory failure   1/62 (1.61%)  1
Surgical and medical procedures   
Hospitalisation   12/62 (19.35%)  16
Vascular disorders   
Hypotension   2/62 (3.23%)  2
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 0%
Treatment (Reduced Intensity Allogeneic Stem Cell Transplant)
Affected / at Risk (%) # Events
Total   0/62 (0.00%)    
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: Senior Administrator, Compliance - Clinical Research Services
Organization: Roswell Park Cancer Institute
Phone: 716-845-2300
Layout table for additonal information
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00856388     History of Changes
Other Study ID Numbers: I 118807
NCI-2009-01508 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: March 4, 2009
First Posted: March 5, 2009
Results First Submitted: May 5, 2016
Results First Posted: June 13, 2016
Last Update Posted: December 5, 2018