Trial Outcomes & Findings for Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders (NCT NCT00301834)

NCT ID: NCT00301834

Last Updated: 2017-09-28

Results Overview

Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: 6 weeks post-transplant
• Results posted on: 2017-09-28

Participant Flow

Subjects recruited from 9/2005 through 9/2010. Patients identified by the Pediatric BMT (Bone Marrow Transplant) Program and consented by study investigators as outpatients in the BMT clinic.

Patients were ineligible if a cord blood was being used for the transplant or if they met any of the other ineligibility criteria in the protocol or did not meet eligibility criteria such as having Fanconi's Anemia.

Participant milestones

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol All eligible patients received pre-transplant conditioning with Alemtuzumab, fludarabine and targeted busulfan followed by allogeneic transplant. The initial dose of busulfan was determined by performing PK (pharmacokinetics) analysis on a test dose of busulfan on the day prior to initiating conditioning. Based on the PK results a starting dose of busulfan was determined. A second PK study was done after the starting dose to ensure that the targeted dose was achieved. If it wasn't achieved, then a dose modification was made and a third PK study done.
Overall Study STARTED	35
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Single Arm - Transplant Pre-conditioning Per Study Protocol All eligible patients received pre-transplant conditioning with Alemtuzumab, fludarabine and targeted busulfan followed by allogeneic transplant. The initial dose of busulfan was determined by performing PK (pharmacokinetics) analysis on a test dose of busulfan on the day prior to initiating conditioning. Based on the PK results a starting dose of busulfan was determined. A second PK study was done after the starting dose to ensure that the targeted dose was achieved. If it wasn't achieved, then a dose modification was made and a third PK study done.

Overall Study Death

1

Baseline Characteristics

Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders

Baseline characteristics by cohort

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 Participants All eligible patients received pre-transplant conditioning with Alemtuzumab, fludarabine and targeted busulfan followed by allogeneic transplant. The initial dose of busulfan was determined by performing PK (pharmacokinetics) analysis on a test dose of busulfan on the day prior to initiating conditioning. Based on the PK results a starting dose of busulfan was determined. A second PK study was done after the starting dose to ensure that the targeted dose was achieved. If it wasn't achieved, then a dose modification was made and a third PK study done.
Age, Categorical <=18 years	34 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	7.58 years STANDARD_DEVIATION 5.25 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Region of Enrollment United States	35 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks post-transplant

Population: Participants evaluable for engraftment 6 weeks post-transplant; 1 patient died of transplant-related hemorrhage prior to 6 weeks and was not evaluated for this outcome

Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences

Outcome measures

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=34 Participants Conditioning with Alemtuzumab, busulfan and fludarabine followed by allogeneic hematopoietic cell transplant.	CMV Seropositive Participants "seropositivity" means the presence of anti-CMV IgG, indicating past infection by the virus
Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation	31 participants	—

SECONDARY outcome

Timeframe: 100 days and 1 year

Outcome measures

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 Participants Conditioning with Alemtuzumab, busulfan and fludarabine followed by allogeneic hematopoietic cell transplant.	CMV Seropositive Participants "seropositivity" means the presence of anti-CMV IgG, indicating past infection by the virus
Treatment-related Mortality at 100 Days and 1 Year Post Transplantation Transplantation-related mortality 0-100 days	2 participants	—
Treatment-related Mortality at 100 Days and 1 Year Post Transplantation Transplantation-related mortality 100-365 days	1 participants	—

SECONDARY outcome

Timeframe: 1 year post-transplantation

Outcome measures

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 Participants Conditioning with Alemtuzumab, busulfan and fludarabine followed by allogeneic hematopoietic cell transplant.	CMV Seropositive Participants "seropositivity" means the presence of anti-CMV IgG, indicating past infection by the virus
Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation Grade 3-4 acute Graft-Versus-Host Disease	2 participants	—
Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation Grade 3-4 mucositis	16 participants	—

SECONDARY outcome

Timeframe: Up to one year post-transplant

Population: 4 participants were incapable of producing Ab or CMV testing result was indeterminate

polymerase chain reaction testing for presence of CMV weekly until at least day +100 then every 2 weeks until T-cell reconstitution as defined by cluster of differentiation 4 (CD4) > 200 cells/mm3. Median time to T-cell reconstitution was 6 months.

Outcome measures

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=14 Participants Conditioning with Alemtuzumab, busulfan and fludarabine followed by allogeneic hematopoietic cell transplant.	CMV Seropositive Participants n=17 Participants "seropositivity" means the presence of anti-CMV IgG, indicating past infection by the virus
Cytomegalovirus (CMV) Viral Infection and Disease Symptoms Positive CMV Viral Load Assay	1 participants	12 participants
Cytomegalovirus (CMV) Viral Infection and Disease Symptoms Symptomatic CMV disease	0 participants	0 participants

SECONDARY outcome

Timeframe: 1 year post-transplantation

Patients deemed "alive and well" at follow-up timepoint later than 1-year post-transplantation

Outcome measures

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 Participants Conditioning with Alemtuzumab, busulfan and fludarabine followed by allogeneic hematopoietic cell transplant.	CMV Seropositive Participants "seropositivity" means the presence of anti-CMV IgG, indicating past infection by the virus
Disease-free Survival With Correction of Disease at One Year Post Transplantation	22 participants	—

Adverse Events

Single Arm - Transplant Pre-conditioning Per Study Protocol

Serious events: 7 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 participants at risk All eligible patients received pre-transplant conditioning with Alemtuzumab, fludarabine and targeted busulfan followed by allogeneic transplant. The initial dose of busulfan was determined by performing PK (pharmacokinetics) analysis on a test dose of busulfan on the day prior to initiating conditioning. Based on the PK results a starting dose of busulfan was determined. A second PK study was done after the starting dose to ensure that the targeted dose was achieved. If it wasn't achieved, then a dose modification was made and a third PK study done.
General disorders aGVHD (acute Graft-Versus-Host Disease)	2.9% 1/35 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory distress associated with Cytomegalovirus infection	2.9% 1/35 • Number of events 1
Blood and lymphatic system disorders Pancytopenia and splenomegaly	2.9% 1/35 • Number of events 1
Respiratory, thoracic and mediastinal disorders Repiratory failure following ideopathic pneumonia syndrome	2.9% 1/35 • Number of events 1
Blood and lymphatic system disorders Thrombocytopenia	2.9% 1/35 • Number of events 1
Infections and infestations Aspergillus pneumonia	2.9% 1/35 • Number of events 1
Renal and urinary disorders Renal Failure	2.9% 1/35 • Number of events 1
Blood and lymphatic system disorders Graft rejection/failure	2.9% 1/35 • Number of events 1
Infections and infestations Viral Encephalitis	2.9% 1/35 • Number of events 1
Vascular disorders Massive intracranial bleed	2.9% 1/35 • Number of events 1

Other adverse events

Measure	Single Arm - Transplant Pre-conditioning Per Study Protocol n=35 participants at risk All eligible patients received pre-transplant conditioning with Alemtuzumab, fludarabine and targeted busulfan followed by allogeneic transplant. The initial dose of busulfan was determined by performing PK (pharmacokinetics) analysis on a test dose of busulfan on the day prior to initiating conditioning. Based on the PK results a starting dose of busulfan was determined. A second PK study was done after the starting dose to ensure that the targeted dose was achieved. If it wasn't achieved, then a dose modification was made and a third PK study done.
Gastrointestinal disorders Mucositis (All grades)	94.3% 33/35 • Number of events 33
General disorders aGVHD	14.3% 5/35 • Number of events 5
General disorders cGVHD (Chronic graft-versus-host disease)	5.7% 2/35 • Number of events 2
General disorders Infusion reaction to alemtuzumab	54.3% 19/35 • Number of events 19

Additional Information

Dr. Morton Cowan

University of California San Francisco

Phone: 4154762188

Email: mcowan@peds.ucsf.edu

Results disclosure agreements

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