Trial Outcomes & Findings for Fludarabine-IV Busulfan ± Clofarabine and Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) (NCT NCT01471444)

Last Updated: 2021-12-16

Results Overview

Number of events with progression free survival. (Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.) or expired from treatment related mortality post transplant.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

256 participants

Primary outcome timeframe

From day of transplant to disease of progression or death of any cause, whichever came first, assessed up to 5 years

Results posted on

2021-12-16

Participant Flow

Participants recruitment from November 2011 to August 2015 at MD Anderson Cancer Center

Participant milestones

Participant milestones
Measure	Arm A (Flu+Bu) Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Overall Study STARTED	133	123
Overall Study COMPLETED	130	120
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Flu+Bu) Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Overall Study Physician Decision	3	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Fludarabine-IV Busulfan ± Clofarabine and Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Flu+Bu) n=130 Participants Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 Participants FlFludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.	Total n=250 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	105 Participants n=5 Participants	103 Participants n=7 Participants	208 Participants n=5 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	15 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	55 Participants n=7 Participants	109 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	65 Participants n=7 Participants	141 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	120 Participants n=5 Participants	114 Participants n=7 Participants	234 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	127 Participants n=5 Participants	119 Participants n=7 Participants	246 Participants n=5 Participants
Region of Enrollment Saudi Arabia	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Qatar	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From day of transplant to disease of progression or death of any cause, whichever came first, assessed up to 5 years

Outcome measures

Outcome measures
Measure	Arm A (Flu+Bu) n=130 Participants Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 Participants Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Progression-Free Survival (PFS)	69 Number of events	61 Number of events

SECONDARY outcome

Timeframe: Post transplant after 1, 3 and 5 years

Number of participants in the study who are alive and disease free at 1, 3 and 5 years post transplant.

Outcome measures

Outcome measures
Measure	Arm A (Flu+Bu) n=130 Participants Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 Participants Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Overall Survival (OS) Post Transplant at 1, 3 and 5 Years 1 Year Post Transplant	83 Participants	82 Participants
Overall Survival (OS) Post Transplant at 1, 3 and 5 Years 3 Year Post Transplant	69 Participants	69 Participants
Overall Survival (OS) Post Transplant at 1, 3 and 5 Years 5 Year Post Transplant	64 Participants	63 Participants

SECONDARY outcome

Timeframe: 100 days post transplant

Number of participants in the study who are with no Grade 3 or 4 acute graft-versus-host disease at any time during the first 100 days post transplant.

Outcome measures

Outcome measures
Measure	Arm A (Flu+Bu) n=130 Participants Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 Participants Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Number of Participants in the Study Who Are With no Grade 3 or 4 Acute Graft-versus-host Disease at Any Time During the First 100 Days Post Transplant.	125 Participants	115 Participants

SECONDARY outcome

Timeframe: 100 day Post Transplant

Number of participants expired from complications other than relapsed disease at 100 day Post Transplant.

Outcome measures

Outcome measures
Measure	Arm A (Flu+Bu) n=130 Participants Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 Participants Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Number of Participants With Non Relapse Mortality at 100 Day Post Transplant	3 Participants	6 Participants

Adverse Events

Arm A (Flu+Bu)

Serious events: 25 serious events

Other events: 123 other events

Deaths: 67 deaths

Arm B (Flu+Clo+Bu)

Serious events: 39 serious events

Other events: 120 other events

Deaths: 59 deaths

Serious adverse events

Other adverse events

Additional Information

Richard Champlin, MD / Stem Cell Transplantation

University of Texas MD Anderson Cancer Center

Phone: 713-792-3618

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A (Flu+Bu) n=130 participants at risk Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 participants at risk Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Gastrointestinal disorders GI GvHD	1.5% 2/130 • Through study completion, an average of 5 years.	3.3% 4/120 • Through study completion, an average of 5 years.
Skin and subcutaneous tissue disorders Skin GVHD	1.5% 2/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
Infections and infestations Bacterial Infections	1.5% 2/130 • Through study completion, an average of 5 years.	7.5% 9/120 • Through study completion, an average of 5 years.
Infections and infestations Viral Infections	3.1% 4/130 • Through study completion, an average of 5 years.	2.5% 3/120 • Through study completion, an average of 5 years.
Infections and infestations Fungal Infections	1.5% 2/130 • Through study completion, an average of 5 years.	3.3% 4/120 • Through study completion, an average of 5 years.
Infections and infestations BK virus associated hemorrhagic cystitis	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.77% 1/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
General disorders Diffused alveolar hemorrhage	1.5% 2/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
General disorders Fluid overload	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders Transcient secondary graft failure	0.77% 1/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders Thrombocytopenia	1.5% 2/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
Vascular disorders Pulmonary embolism	0.00% 0/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
Vascular disorders DIC	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders Elevated transminitis	0.77% 1/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders Ascites	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders VOD/SOS	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders Liver GvHD	1.5% 2/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Nervous system disorders Encephalopathy	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders Poor graft function	1.5% 2/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders ABO incompatibility	0.77% 1/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.
Investigations Hemochromatosis	0.77% 1/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.

Measure	Arm A (Flu+Bu) n=130 participants at risk Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.	Arm B (Flu+Clo+Bu) n=120 participants at risk Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0.
Infections and infestations Infections	79.2% 103/130 • Through study completion, an average of 5 years.	74.2% 89/120 • Through study completion, an average of 5 years.
Investigations ATG induced fevers	50.0% 65/130 • Through study completion, an average of 5 years.	34.2% 41/120 • Through study completion, an average of 5 years.
Immune system disorders Allergic reaction to ATG	1.5% 2/130 • Through study completion, an average of 5 years.	3.3% 4/120 • Through study completion, an average of 5 years.
General disorders Fluid overload	44.6% 58/130 • Through study completion, an average of 5 years.	45.0% 54/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders ABO incompatibility	3.1% 4/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders GI GvHD	13.8% 18/130 • Through study completion, an average of 5 years.	14.2% 17/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders Mucositis	94.6% 123/130 • Through study completion, an average of 5 years.	95.8% 115/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders Upper GI GvHD	26.9% 35/130 • Through study completion, an average of 5 years.	33.3% 40/120 • Through study completion, an average of 5 years.
Renal and urinary disorders Renal insufficiency	21.5% 28/130 • Through study completion, an average of 5 years.	20.8% 25/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders Liver GvHD	19.2% 25/130 • Through study completion, an average of 5 years.	17.5% 21/120 • Through study completion, an average of 5 years.
Eye disorders Chronic ocular GvHD	17.7% 23/130 • Through study completion, an average of 5 years.	16.7% 20/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders Chronic oral GvHD	15.4% 20/130 • Through study completion, an average of 5 years.	15.8% 19/120 • Through study completion, an average of 5 years.
Respiratory, thoracic and mediastinal disorders Chronic lung GvGHD	6.9% 9/130 • Through study completion, an average of 5 years.	5.8% 7/120 • Through study completion, an average of 5 years.
Investigations Neutropenic fevers	32.3% 42/130 • Through study completion, an average of 5 years.	39.2% 47/120 • Through study completion, an average of 5 years.
Cardiac disorders Cardiomyopathy	1.5% 2/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.
Cardiac disorders Dysrhythmia	3.1% 4/130 • Through study completion, an average of 5 years.	2.5% 3/120 • Through study completion, an average of 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	11.5% 15/130 • Through study completion, an average of 5 years.	15.0% 18/120 • Through study completion, an average of 5 years.
Skin and subcutaneous tissue disorders Skin GvHD	54.6% 71/130 • Through study completion, an average of 5 years.	69.2% 83/120 • Through study completion, an average of 5 years.
Vascular disorders Hypertension	29.2% 38/130 • Through study completion, an average of 5 years.	30.8% 37/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders Ascites	1.5% 2/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders Diarrhea	31.5% 41/130 • Through study completion, an average of 5 years.	42.5% 51/120 • Through study completion, an average of 5 years.
Gastrointestinal disorders Nausea	94.6% 123/130 • Through study completion, an average of 5 years.	100.0% 120/120 • Through study completion, an average of 5 years.
Renal and urinary disorders Hemorrhagic cystits	1.5% 2/130 • Through study completion, an average of 5 years.	0.00% 0/120 • Through study completion, an average of 5 years.
Infections and infestations BK virus associated hemorrhagic cystitis	15.4% 20/130 • Through study completion, an average of 5 years.	22.5% 27/120 • Through study completion, an average of 5 years.
General disorders Elevated transminitis	81.5% 106/130 • Through study completion, an average of 5 years.	100.0% 120/120 • Through study completion, an average of 5 years.
Nervous system disorders PRES	0.77% 1/130 • Through study completion, an average of 5 years.	2.5% 3/120 • Through study completion, an average of 5 years.
Nervous system disorders Headaches	7.7% 10/130 • Through study completion, an average of 5 years.	10.8% 13/120 • Through study completion, an average of 5 years.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia	8.5% 11/130 • Through study completion, an average of 5 years.	10.0% 12/120 • Through study completion, an average of 5 years.
Skin and subcutaneous tissue disorders ATG induced skin rash	14.6% 19/130 • Through study completion, an average of 5 years.	6.7% 8/120 • Through study completion, an average of 5 years.
Skin and subcutaneous tissue disorders Rash	10.8% 14/130 • Through study completion, an average of 5 years.	15.0% 18/120 • Through study completion, an average of 5 years.
Nervous system disorders Confusions	0.00% 0/130 • Through study completion, an average of 5 years.	7.5% 9/120 • Through study completion, an average of 5 years.
General disorders Fevers	0.00% 0/130 • Through study completion, an average of 5 years.	14.2% 17/120 • Through study completion, an average of 5 years.
Hepatobiliary disorders VOD/SOS	0.00% 0/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
Investigations autoimmune hemolytic anemia	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/130 • Through study completion, an average of 5 years.	1.7% 2/120 • Through study completion, an average of 5 years.
Vascular disorders Pulmonary embolism	0.00% 0/130 • Through study completion, an average of 5 years.	0.83% 1/120 • Through study completion, an average of 5 years.