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Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT01529827
Recruitment Status : Active, not recruiting
First Posted : February 9, 2012
Results First Posted : July 2, 2017
Last Update Posted : March 26, 2019
Sponsor:
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
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 Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Aplastic Anemia
Burkitt Lymphoma
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Myelomonocytic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Congenital Amegakaryocytic Thrombocytopenia
Diamond-Blackfan Anemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Paroxysmal Nocturnal Hemoglobinuria
Peripheral T-cell Lymphoma
Polycythemia Vera
Post-transplant Lymphoproliferative Disorder
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 Hairy Cell Leukemia
Refractory Multiple Myeloma
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Secondary Myelofibrosis
Severe Combined Immunodeficiency
Severe Congenital Neutropenia
Shwachman-Diamond Syndrome
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Waldenstrom Macroglobulinemia
Wiskott-Aldrich Syndrome
Interventions Drug: fludarabine phosphate
Drug: melphalan
Radiation: total-body irradiation
Drug: tacrolimus
Drug: mycophenolate mofetil
Drug: methotrexate
Other: laboratory biomarker analysis
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Enrollment 94
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Period Title: Overall Study
Started 94
Completed 94
Not Completed 0
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Overall Number of Baseline Participants 94
Hide Baseline Analysis Population Description
All treated and eligible patients
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants
<=18 years
1
   1.1%
Between 18 and 65 years
66
  70.2%
>=65 years
27
  28.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 94 participants
57.2  (12.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants
Female
45
  47.9%
Male
49
  52.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 94 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   1.1%
White
93
  98.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Transplant Related Mortality (TRM)
Hide Description Day 100 transplant related mortality (TRM). An exact 95% confidence interval will be provided.
Time Frame In the first 100 days from day 0 of transplant
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Overall Number of Participants Analyzed 94
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.5
(4.0 to 15.3)
2.Secondary Outcome
Title Clinical Response
Hide Description

Patients will be followed according to response criteria as referenced in BMT SOP "Standards of Therapy" last updated 2008. Clinical Response = CR + PR.

Complete Response Requires all of the following:

  • Serum and urine negative for monoclonal proteins by immunofixation
  • Normal free light chain ratio
  • Plasma cells in marrow < 5%

Partial Response (PR) Requires any of the following:

- ≥ 50% reduction in current serum monoclonal protein levels > 0.5 g/dL or urine light chain levels > 100 mg/day with a visible peak or free light chain levels > 10mg/dL

Progressive Disease (PD) Requires any of the following:

  • If progressing from CR, any detectable monoclonal protein or abnormal free light chain ratio (light chain must double)
  • If progressive from PR or SD, ≥ 50% increase in the serum M protein to > 0.5 g/dL,or ≥ 50% increase in urine M protein to > 200mg/day with visible peak present.
  • Free light chain increase of ≥ 50% to
Time Frame In the first 100 days from day 0 of transplant
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Overall Number of Participants Analyzed 94
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
45
(34 to 55)
3.Secondary Outcome
Title Progression Free Survival (PFS) at One Year
Hide Description Assessed using Kaplan Meier and Proportional Hazards
Time Frame day of transplant until progression up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
All treated and eligible patients
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Overall Number of Participants Analyzed 94
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
85
(76 to 91)
4.Secondary Outcome
Title Median Time to Neutrophil Engraftment
Hide Description Median time to recovery of absolute neutrophil count >=500/uL for 3 consecutive days. 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 PBSCT)
Hide Arm/Group Description:

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

Overall Number of Participants Analyzed 94
Median (Full Range)
Unit of Measure: days
17
(6 to 64)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Reduced Intensity Allogeneic PBSCT)
Hide Arm/Group Description

PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan IV over 30 minutes on day -2. Patients undergo low-dose TBI BID on day -1. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. GvHD PROPHYLAXIS: Patients receive tacrolimus IV or PO BID on days -1 to 100 with taper over 4-6 months, MMF PO or IV every 6-8 hours on days -1 to 60, and methotrexate IV over 15 to 30 minutes on days 1, 3, and 6.

fludarabine phosphate: Given IV

melphalan: Given IV

total-body irradiation: Undergo TBI

tacrolimus: Given IV or PO

mycophenolate mofetil: Given IV or PO

methotrexate: Given IV

laboratory biomarker analysis: Correlative studies

allogeneic hematopoietic stem cell transplantation: Undergo allogeneic PBSCT

peripheral blood stem cell transplantation: Undergo PBSCT

All-Cause Mortality
Treatment (Reduced Intensity Allogeneic PBSCT)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Reduced Intensity Allogeneic PBSCT)
Affected / at Risk (%) # Events
Total   17/94 (18.09%)    
Cardiac disorders   
Myocardial infarction   1/94 (1.06%)  4
General disorders   
Multi-organ failure   1/94 (1.06%)  8
Pyrexia   2/94 (2.13%)  22
Immune system disorders   
Acute graft versus host disease in intestine   2/94 (2.13%)  18
Graft versus host disease   3/94 (3.19%)  13
Infections and infestations   
Infection   1/94 (1.06%)  5
Pneumonia   1/94 (1.06%)  8
Investigations   
Blood culture positive   1/94 (1.06%)  4
Gram stain positive   1/94 (1.06%)  4
Metabolism and nutrition disorders   
Decreased appetite   1/94 (1.06%)  4
Musculoskeletal and connective tissue disorders   
Muscular weakness   1/94 (1.06%)  4
Respiratory, thoracic and mediastinal disorders   
Pleuritic pain   1/94 (1.06%)  4
Surgical and medical procedures   
Hospitalisation   1/94 (1.06%)  4
Vascular disorders   
Hypotension   1/94 (1.06%)  8
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 PBSCT)
Affected / at Risk (%) # Events
Total   1/94 (1.06%)    
Immune system disorders   
Acute graft versus host disease in intestine   1/94 (1.06%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Senior Administrator, Compliance - Clinical Research Services
Organization: Roswell Park Cancer Institute
Phone: 716-845-2300
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01529827     History of Changes
Other Study ID Numbers: I 177110
NCI-2011-03563 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: February 6, 2012
First Posted: February 9, 2012
Results First Submitted: June 30, 2017
Results First Posted: July 2, 2017
Last Update Posted: March 26, 2019