Trial Outcomes & Findings for Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies (NCT NCT01529827)

NCT ID: NCT01529827

Last Updated: 2019-09-24

Results Overview

Day 100 transplant related mortality (TRM). An exact 95% confidence interval will be provided.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 94 participants
• Primary outcome timeframe: In the first 100 days from day 0 of transplant
• Results posted on: 2019-09-24

Participant Flow

Participant milestones

Measure	Treatment (Reduced Intensity Allogeneic PBSCT) 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 Study STARTED	94
Overall Study COMPLETED	94
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (Reduced Intensity Allogeneic PBSCT) n=94 Participants 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
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	66 Participants n=5 Participants
Age, Categorical >=65 years	27 Participants n=5 Participants
Age, Continuous	57.2 years STANDARD_DEVIATION 12.3 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	93 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: In the first 100 days from day 0 of transplant

Population: All treated and eligible patients

Day 100 transplant related mortality (TRM). An exact 95% confidence interval will be provided.

Outcome measures

Measure

Treatment (Reduced Intensity Allogeneic PBSCT) n=94 Participants 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

Transplant Related Mortality (TRM)

8.5 percentage of participants Interval 4.0 to 15.3

SECONDARY outcome

Timeframe: In the first 100 days from day 0 of transplant

Population: All treated and eligible patients

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

Outcome measures

Measure

Treatment (Reduced Intensity Allogeneic PBSCT) n=94 Participants 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

Clinical Response

45 percentage of participants Interval 34.0 to 55.0

SECONDARY outcome

Timeframe: day of transplant until progression up to 5 years

Population: All treated and eligible patients

Assessed using Kaplan Meier and Proportional Hazards

Outcome measures

Measure

Treatment (Reduced Intensity Allogeneic PBSCT) n=94 Participants 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

Progression Free Survival (PFS) at One Year

85 percentage of participants Interval 76.0 to 91.0

SECONDARY outcome

Timeframe: Day 100

Population: All treated and eligible patients

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.

Outcome measures

Measure

Treatment (Reduced Intensity Allogeneic PBSCT) n=94 Participants 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

Median Time to Neutrophil Engraftment

17 days Interval 6.0 to 64.0

Adverse Events

Treatment (Reduced Intensity Allogeneic PBSCT)

Serious events: 17 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment (Reduced Intensity Allogeneic PBSCT) n=94 participants at risk 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
Cardiac disorders Myocardial infarction	1.1% 1/94 • Number of events 4
General disorders Multi-organ failure	1.1% 1/94 • Number of events 8
General disorders Pyrexia	2.1% 2/94 • Number of events 22
Immune system disorders Acute graft versus host disease in intestine	2.1% 2/94 • Number of events 18
Immune system disorders Graft versus host disease	3.2% 3/94 • Number of events 13
Infections and infestations Infection	1.1% 1/94 • Number of events 5
Infections and infestations Pneumonia	1.1% 1/94 • Number of events 8
Investigations Blood culture positive	1.1% 1/94 • Number of events 4
Investigations Gram stain positive	1.1% 1/94 • Number of events 4
Metabolism and nutrition disorders Decreased appetite	1.1% 1/94 • Number of events 4
Musculoskeletal and connective tissue disorders Muscular weakness	1.1% 1/94 • Number of events 4
Respiratory, thoracic and mediastinal disorders Pleuritic pain	1.1% 1/94 • Number of events 4
Surgical and medical procedures Hospitalisation	1.1% 1/94 • Number of events 4
Vascular disorders Hypotension	1.1% 1/94 • Number of events 8

Other adverse events

Measure

Treatment (Reduced Intensity Allogeneic PBSCT) n=94 participants at risk 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

Immune system disorders Acute graft versus host disease in intestine

1.1% 1/94 • Number of events 1

Additional Information

Senior Administrator, Compliance - Clinical Research Services

Roswell Park Cancer Institute

Phone: 716-845-2300

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place