Trial Outcomes & Findings for Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer (NCT NCT00245037)
NCT ID: NCT00245037
Last Updated: 2017-09-27
Results Overview
Non-hematologic toxicities and adverse experiences ≥ Grade 3 occurrences measured up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant. The following data represents the number of regimen-related, grade 3 and 4 toxicities that occurred in each category.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
147 participants
Primary outcome timeframe
5 years post-transplant
Results posted on
2017-09-27
Participant Flow
Participant milestones
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Overall Study
STARTED
|
147
|
|
Overall Study
COMPLETED
|
130
|
|
Overall Study
NOT COMPLETED
|
17
|
Reasons for withdrawal
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
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|---|---|
|
Overall Study
Death
|
17
|
Baseline Characteristics
Eight patients did not have KPS status available, which is why the values do not add up to the total number of participants.
Baseline characteristics by cohort
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=147 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
81 Participants
n=147 Participants
|
|
Age, Categorical
>=65 years
|
66 Participants
n=147 Participants
|
|
Sex: Female, Male
Female
|
49 Participants
n=147 Participants
|
|
Sex: Female, Male
Male
|
98 Participants
n=147 Participants
|
|
Karnofsky Performance Score (KPS)
KPS ≥ 90
|
91 Participants
n=139 Participants • Eight patients did not have KPS status available, which is why the values do not add up to the total number of participants.
|
|
Karnofsky Performance Score (KPS)
KPS < 90
|
48 Participants
n=139 Participants • Eight patients did not have KPS status available, which is why the values do not add up to the total number of participants.
|
|
Pre-Transplant Disease Status
In Complete Remission
|
85 Participants
n=147 Participants
|
|
Pre-Transplant Disease Status
Not in Complete Remission
|
62 Participants
n=147 Participants
|
|
Disease Risk Index (DRI)
Low or intermediate
|
93 Participants
n=144 Participants • DRI was unclassifiable in 3 patients.
|
|
Disease Risk Index (DRI)
High or Very High
|
51 Participants
n=144 Participants • DRI was unclassifiable in 3 patients.
|
|
HLA Match
8/8
|
135 Participants
n=147 Participants
|
|
HLA Match
7/8
|
12 Participants
n=147 Participants
|
|
Donor Relation
Related Sibling Donor
|
39 Participants
n=147 Participants
|
|
Donor Relation
Unrelated Donor
|
108 Participants
n=147 Participants
|
|
Cytomegalovirus (CMV) Status
-/- recipient/donor
|
22 Participants
n=140 Participants • Cytomegalovirus (CMV) status was unavailable in 7 patients.
|
|
Cytomegalovirus (CMV) Status
All other combinations
|
118 Participants
n=140 Participants • Cytomegalovirus (CMV) status was unavailable in 7 patients.
|
|
Donor/Recipient Gender
F/F, M/M, M/F
|
117 Participants
n=147 Participants
|
|
Donor/Recipient Gender
F/M
|
30 Participants
n=147 Participants
|
PRIMARY outcome
Timeframe: 5 years post-transplantNon-hematologic toxicities and adverse experiences ≥ Grade 3 occurrences measured up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant. The following data represents the number of regimen-related, grade 3 and 4 toxicities that occurred in each category.
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Regimen-Related Toxicities
Cardiac Disorders
|
21 Toxicities
|
|
Regimen-Related Toxicities
Renal Disorders
|
10 Toxicities
|
|
Regimen-Related Toxicities
Respiratory Disorders
|
8 Toxicities
|
|
Regimen-Related Toxicities
CNS Disorders
|
16 Toxicities
|
|
Regimen-Related Toxicities
Hepatic Disorders
|
39 Toxicities
|
|
Regimen-Related Toxicities
General Disorders
|
30 Toxicities
|
PRIMARY outcome
Timeframe: Two years post-transplantPercent of subjects with non-relapse mortality two years after conditioning with busulfan with fludarabine/200 cGy TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease.
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Non-relapse Mortality
Year 1
|
27 Participants
|
|
Non-relapse Mortality
Year 2
|
33 Participants
|
SECONDARY outcome
Timeframe: Years 1, 2, 3 and 5The percentage of overall patient survival (out of 147 participants) for Years 1, 2, 3 and 5.
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Overall Survival
Year 3
|
42 percentage of analyzed participants
|
|
Overall Survival
Year 1
|
60 percentage of analyzed participants
|
|
Overall Survival
Year 2
|
48 percentage of analyzed participants
|
|
Overall Survival
Year 5
|
29 percentage of analyzed participants
|
SECONDARY outcome
Timeframe: Years 1, 2, 3, and 5The percentage of progression-free patients (out of 147 participants) at Years 1, 2, 3, and 5. Definition of Disease Progression: MM/Plasma Cell: Increasing bone pain or increase in serum/urine monoclonal protein by 25%. CLL/NHL/HD: New sites of lymphadenopathy; ≥ 25% increase in lymph node size; Blood or bone marrow involvement with clonal B-cells; Increase of ≥ 25% bone marrow involvement; ≥ 25% increase in blood involvement with clonal B-cells. AML/ALL: Any incidence of relapse (\>5% blasts) by evaluation of the bone marrow aspirate. CML: Inability to control platelet or granulocyte counts; Increase in baseline number of metaphases demonstrating the Ph+ chromosome by \>25%; Any other new cytogenetic abnormality; Transformation to accelerated phase or blast crisis. MDS/MPD: Any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of new blasts (\>5%) or worsening cytopenia or cytogenetic evidence of recurrence.
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Progression-Free Survival
Year 1
|
48 percentage of analyzed participants
|
|
Progression-Free Survival
Year 2
|
39 percentage of analyzed participants
|
|
Progression-Free Survival
Year 3
|
35 percentage of analyzed participants
|
|
Progression-Free Survival
Year 5
|
29 percentage of analyzed participants
|
SECONDARY outcome
Timeframe: Years 1 and 2The percentage of patients (out of 147 participants) who relapsed at Years 1 and 2. Relapse is defined as the presence of \>5% blasts by morphology on a post-transplant bone marrow aspirate.
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Relapse Mortality
Year 1
|
13 percentage of analyzed participants
|
|
Relapse Mortality
Year 2
|
20 percentage of analyzed participants
|
SECONDARY outcome
Timeframe: Day 100, Month 6Population: This is cumulative incidence of grades 2-4 aGVHD at 100 days and at 6 months. Out of the total number of participants, grades 2-4 aGVHD occurred in 79 patients.
Grading of Acute GVHD: Severity of Individual Organ Involvement: Skin * 1 a maculopapular eruption involving less than 25% of the body surface * 2 a maculopapular eruption involving 25-50% of the body surface * 3 generalized erythroderma * 4 generalized erythroderma with bullous formation and/or with desquamation Liver * 1 bilirubin 2.0-3.0mg/100mL * 2 bilirubin 3-5.9mg/100mL * 3 bilirubin 6-14.9mg/100mL * 4 bilirubin \>15mg/100mL Gut Diarrhea is graded +1 to +4 in severity. Nausea/vomiting and/or anorexia caused by GVHD is assigned as +1 in severity Diarrhea * 1 \<1000mL of liquid stool/day * 2 \>1,000mL of stool/day * 3 \>1,500mL of stool/day * 4 2,000mL of stool/day, severe abdominal pain, with or without ileus Severity of GVHD: Grade 1 +1 to +2 skin rash; No gut or liver involvement Grade 2 +1 to +3 skin rash;+1 GI involvement and/or +1 liver
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Acute Graft-Versus-Host Disease (aGVHD) Outcome
Day 100
|
55 percentage of analyzed participants
|
|
Acute Graft-Versus-Host Disease (aGVHD) Outcome
Month 6
|
60 percentage of analyzed participants
|
SECONDARY outcome
Timeframe: Years 1, 2 and 3Population: This is a cumulative incidence of cGVHD at 1 year, 2 years, and 3 years. A total of 99 patients (out of 147) developed cGVHD, 86 patients (87%) with extensive stage cGVHD and 13 patients (13%) with limited stage cGVHD.
Grading of Chronic GVHD: Limited: Localized skin involvement and/or hepatic dysfunction due to chronic GVHD Extensive: One or more of the following: Generalized skin involvement Liver histology showing chronic aggressive hepatitis, bridging necrosis or cirrhosis Involvement of the eye: Schirmer's test with \<5 mm wetting Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy Involvement of any other target organ Chronic GVHD Severity: Mild: Signs and symptoms of cGVHD do not interfere substantially with function and do not progress once appropriately treated with local therapy or standard systemic therapy. Moderate: Signs and symptoms of cGVHD interfere somewhat with function despite appropriate therapy or are progressive through first line systemic therapy. Severe: Signs and symptoms of cGVHD limit function substantially despite appropriate therapy or are progressive through second line systemic therapy
Outcome measures
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 Participants
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Chronic Graft-Versus-Host Disease (cGVHD) Outcome
Year 1
|
64.6 percentage of analyzed participants
|
|
Chronic Graft-Versus-Host Disease (cGVHD) Outcome
Year 2
|
66 percentage of analyzed participants
|
|
Chronic Graft-Versus-Host Disease (cGVHD) Outcome
Year 3
|
67.3 percentage of analyzed participants
|
Adverse Events
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
Serious events: 59 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 participants at risk
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Cardiac disorders
Pericardial effusion
|
1.4%
2/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Cardiac disorders
Atrial fibrillation/flutter
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Cardiac disorders
Respiratory pulseless electrical activity (PEA) arrest
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Renal and urinary disorders
Event associated with CsA
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Respiratory, thoracic and mediastinal disorders
Cryptogenic organizing pneumonia
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Respiratory, thoracic and mediastinal disorders
Eosinophilic pneumonia
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Nervous system disorders
CsA toxicity
|
3.4%
5/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Nervous system disorders
Posterior-reversible encephalopathy syndrome
|
1.4%
2/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Hepatobiliary disorders
Veno-occlusive disease
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Iron overload
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Steroid myopathy
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Hemolysis
|
3.4%
5/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
ABO incompatability
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Bleeding
|
1.4%
2/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Thrombosis/deep vein thrombosis
|
3.4%
5/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Thrombotic thrombocytopenic purpura (TTP)
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Refractory ascites
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
General disorders
Ogilvie's syndrome
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Musculoskeletal and connective tissue disorders
Fractures/musculoskeletal
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Infections and infestations
Death Caused by Bacterial Infection
|
4.8%
7/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Infections and infestations
Death Caused by Fungal Infection
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Infections and infestations
Death Caused by Sepsis/Septic Shock
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Infections and infestations
Death Caused by Viral Infection
|
2.0%
3/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Infections and infestations
Death Caused by Nonspecified Pneumonia
|
0.68%
1/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
Other adverse events
| Measure |
Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI)
n=147 participants at risk
Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0
Therapeutic allogeneic lymphocytes: A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
Busulfan: Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV Busulfan is available and diluted and administered per package insert guidelines.
Cyclosporine: Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including
|
|---|---|
|
Infections and infestations
Neutropenic fever
|
9.5%
14/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
|
Hepatobiliary disorders
Hyperbilirubinemia or transaminitis
|
25.9%
38/147 • Non-hematologic toxicities and adverse experiences ≥ Grade 3 will be assessed up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant.
|
Additional Information
Richard T. Maziarz, MD
Oregon Health and Science University
Phone: 503-494-6345
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place