Trial Outcomes & Findings for Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies (NCT NCT01499147)
NCT ID: NCT01499147
Last Updated: 2018-11-08
Results Overview
Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
100 participants
Primary outcome timeframe
Up to 30 days post-transplant
Results posted on
2018-11-08
Participant Flow
We analyzed the clinical outcome of patients with hematological malignancies at standard or high-risk, who were transplanted (allogeneic peripheral blood or BMT HSCT) after receiving FluBU as a conditioning regimen. A total of 30 patients were recruited for this study which was conducted at the UIC Medical Center Inpatient BMT unit.
Criteria for FluBu conditioning: \<60 years old; no diagnosis of myeloma or myelofibrosis (MF) in chronic phase; and not having received an autologous stem cell transplant with the last 2 years. Patients not fulfilling these criteria but still eligible for allogeneic transplantation were prepared with FluMel.
Participant milestones
| Measure |
Fludarabine/Busulfan + ATG
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Fludarabine/Melphalan + ATG
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
|---|---|---|
|
Overall Study
STARTED
|
33
|
17
|
|
Overall Study
COMPLETED
|
18
|
12
|
|
Overall Study
NOT COMPLETED
|
15
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
Baseline characteristics by cohort
| Measure |
Arm 1
n=18 Participants
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Arm 2
n=12 Participants
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
34 years
n=5 Participants
|
49 years
n=7 Participants
|
42.5 years
n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
12 participants
n=7 Participants
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 30 days post-transplantMedian time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.
Outcome measures
| Measure |
Fludarabine/Busulfan + ATG
n=18 Participants
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Fludarabine/Melphalan + ATG
n=12 Participants
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
|---|---|---|
|
Number of Participants With Engraftment.
|
18 participants
|
12 participants
|
SECONDARY outcome
Timeframe: Up to 100 days post-transplant.Day 100 transplant-related mortality was measured in both groups.
Outcome measures
| Measure |
Fludarabine/Busulfan + ATG
n=18 Participants
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Fludarabine/Melphalan + ATG
n=12 Participants
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
|---|---|---|
|
Participants With 100 Day Transplant-related Mortality.
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 30 days post-transplantDays to ANC or platelet engraftment
Outcome measures
| Measure |
Fludarabine/Busulfan + ATG
n=18 Participants
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Fludarabine/Melphalan + ATG
n=12 Participants
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
|---|---|---|
|
Time to ANC and Platelet Engraftment
|
15 days to ANC and platelet engraftment
Interval 0.0 to 24.0
|
12 days to ANC and platelet engraftment
Interval 10.0 to 22.0
|
SECONDARY outcome
Timeframe: Up to 100 days post-transplant (acute GVHD).Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.
Outcome measures
| Measure |
Fludarabine/Busulfan + ATG
n=18 Participants
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
fludarabine/busulfan: All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
|
Fludarabine/Melphalan + ATG
n=12 Participants
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
fludarabine/ melphalan: All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 \<40%, DLCO\<50%, LVEF\<40, Serum bilirubin \>1.5 mg% or serum transaminases \> 2x nl).
|
|---|---|---|
|
Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).
|
2 participants
|
1 participants
|
Adverse Events
Participants With Extra-hematological Toxicities
Serious events: 8 serious events
Other events: 0 other events
Deaths: 0 deaths
FluBu Participants With Extra-hematological Toxicities
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
FluMel Participants With Extra-hematological Toxicities
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Participants With Extra-hematological Toxicities
n=30 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and FluMel and receiving PBSC.
|
FluBu Participants With Extra-hematological Toxicities
n=18 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and receiving PBSC.
|
FluMel Participants With Extra-hematological Toxicities
n=12 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluMel and receiving PBSC.
|
|---|---|---|---|
|
Gastrointestinal disorders
stomatitis
|
10.0%
3/30 • Number of events 3 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
11.1%
2/18 • Number of events 2 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
8.3%
1/12 • Number of events 1 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
|
Immune system disorders
CMV reactivation
|
16.7%
5/30 • Number of events 5 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
16.7%
3/18 • Number of events 3 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
16.7%
2/12 • Number of events 2 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
Other adverse events
| Measure |
Participants With Extra-hematological Toxicities
n=30 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and FluMel and receiving PBSC.
|
FluBu Participants With Extra-hematological Toxicities
n=18 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluBu and receiving PBSC.
|
FluMel Participants With Extra-hematological Toxicities
n=12 participants at risk
We analyzed if different rates of severe extra-hematological toxicities could be detected in patients conditioned with FluMel and receiving PBSC.
|
|---|---|---|---|
|
Hepatobiliary disorders
Veno-occlusive disease
|
0.00%
0/30 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
0.00%
0/18 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
0.00%
0/12 • 365 days post-transplant
REGIMEN-RELATED TOXICITY ACCORDING TO ORGAN SYSTEM (ref: Bearman et al: J Clin Oncol vol 6, 1988, 1562-1568)
|
Additional Information
Damiano Rondelli, MD
University of Illinois Cancer Center
Phone: 312-996-6179
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place