Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00469014
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 72
• Location: 1
• Arms: 4
• Duration (Months): 78
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia	Drug: Clofarabine; Drug: Busulfan; Drug: Fludarabine; Other: Stem Cell Infusion; Drug: Thymoglobulin (ATG); Drug: Filgrastim	Phase 2

Detailed Description

Busulfan is a chemotherapy drug that kills cancer cells by binding to DNA (the genetic material of cells). Clofarabine is designed to interfere with the growth and development of cancer cells. Fludarabine is designed to interfere with DNA repair enzymes so that the leukemic cells cannot repair damaged DNA. This may increase the likelihood of the cell dying. These drugs are being given to try to kill cancerous cells and weaken your immune system in order to lower the risk of stem cell transplant rejection.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 4 study groups. Three (3) of the groups will receive busulfan, fludarabine, and clofarabine at different dose levels. The 4th group will only receive busulfan and clofarabine. As the study continues, participants will be assigned using a method called adaptive randomization. This method works by increasing the chances of being assigned to the group that has had the best results in the study so far. You will know which group you have been assigned to.

Participants will receive busulfan, fludarabine, and/or clofarabine once a day for 4 doses. You will first receive an additional low-level "test" dose of busulfan given by vein to check how your blood levels change over time. This information will be used to decide the next dose needed to reach a target blood level of busulfan. You will have a total of about 6 and 1/2 tablespoons of blood drawn over time to check your busulfan blood levels following one or more of the busulfan treatments. Up to 11 samples of blood will be drawn to check your blood levels of busulfan during the next 11 hours following the test dose and the first high-dose busulfan treatment. Each sample will require about 1 teaspoon of blood. A heparin lock line will be placed in a vein to lower the number of needle sticks needed for these draws. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard fixed (unchanging) dose of busulfan.

Clofarabine and fludarabine (if applicable) will be given through a central venous catheter (CVC) over 1 hour, once a day, for 4 days. Busulfan will also be given through the CVC over 3 hours.

If you are going to be receiving a transplant from an HLA-nonidentical or unrelated donor, you will also receive thymoglobulin (ATG) over 4 hours on the 3 days before the transplant to further weaken your immune system to reduce the risk of rejecting of the transplant. After the transplant, you will receive tacrolimus, methotrexate, or other immunosuppressive (lowering the immune system) drugs in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body.

The allogeneic stem cells (bone marrow or peripheral blood stem cells) will also be given through the CVC. You will receive the drug G-CSF (filgrastim) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal.

Patients usually stay in the hospital for about 4 weeks after stem cell transplantation. After you are released from the hospital, you will continue to be monitored as an outpatient for infections and transplant-related complications for at least 100 days after the transplant.

You will have blood tests (about 4 tablespoons of blood) and bone marrow aspirations performed at 1, 3, 6, and 12 months after the transplant, to check if the disease is in remission (has not come back). Your health status will be followed with the help of your local doctor to find out if the leukemia or MDS comes back, as well as to check the length of your survival.

This is an investigational study. All of the drugs used in this study are approved by the FDA for treatment of cancer. Busulfan has been approved for use in stem cell transplantation. The use of these drugs together with stem cell transplant is experimental. Up to 70 patients will take part in this study. All will be enrolled at the M. D. Anderson Cancer Center.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Busulfan-Fludarabine-Clofarabine With Allogeneic Stem Cell Transplantation for Advanced Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Advanced, Gleevec Refractory Chronic Myeloid Leukemia. A Randomized Phase II Study.
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine 4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	Drug: Clofarabine; Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily; Other Names: Clofarex Clolar ; Drug: Busulfan; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily. Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.; Other Names: Busulfex Myleran ; Drug: Fludarabine; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Other Names: Fludarabine Phosphate Fludara ; Other: Stem Cell Infusion; Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC)); Other Names: Bone Marrow Transplant BMT peripheral blood progenitor cells PBPC Unstimulated bone marrow transplant bone marrow transplantation ABM transplantations autologous bone marrow transplantation ; Drug: Thymoglobulin (ATG); Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.; Other Names: Thymoglobulin Antithymocyte Globulin ; Drug: Filgrastim; Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.; Other Names: G-CSF Granulocyte colony-stimulating factor GCSF
Experimental: Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine 4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	Drug: Clofarabine; Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily; Other Names: Clofarex Clolar ; Drug: Busulfan; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily. Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.; Other Names: Busulfex Myleran ; Drug: Fludarabine; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Other Names: Fludarabine Phosphate Fludara ; Other: Stem Cell Infusion; Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC)); Other Names: Bone Marrow Transplant BMT peripheral blood progenitor cells PBPC Unstimulated bone marrow transplant bone marrow transplantation ABM transplantations autologous bone marrow transplantation ; Drug: Thymoglobulin (ATG); Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.; Other Names: Thymoglobulin Antithymocyte Globulin ; Drug: Filgrastim; Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.; Other Names: G-CSF Granulocyte colony-stimulating factor GCSF
Experimental: Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine 4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	Drug: Clofarabine; Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily; Other Names: Clofarex Clolar ; Drug: Busulfan; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily. Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.; Other Names: Busulfex Myleran ; Drug: Fludarabine; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Other Names: Fludarabine Phosphate Fludara ; Other: Stem Cell Infusion; Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC)); Other Names: Bone Marrow Transplant BMT peripheral blood progenitor cells PBPC Unstimulated bone marrow transplant bone marrow transplantation ABM transplantations autologous bone marrow transplantation ; Drug: Thymoglobulin (ATG); Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.; Other Names: Thymoglobulin Antithymocyte Globulin ; Drug: Filgrastim; Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.; Other Names: G-CSF Granulocyte colony-stimulating factor GCSF
Experimental: Arm 4: Busulfan + Clofarabine 4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	Drug: Clofarabine; Day -6 to Day -3 for Arm 1 = 10 mg/m^2 intravenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily; Other Names: Clofarex Clolar ; Drug: Busulfan; Day -6 to Day -3 for Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily. Test dose Day -8 32 mg/ m^2 IV over 45 min, rest on Day -7.; Other Names: Busulfex Myleran ; Other: Stem Cell Infusion; Day 0 stem cell infusion (Bone marrow or peripheral blood progenitor cells (PBPC)); Other Names: Bone Marrow Transplant BMT peripheral blood progenitor cells PBPC Unstimulated bone marrow transplant bone marrow transplantation ABM transplantations autologous bone marrow transplantation ; Drug: Thymoglobulin (ATG); Day -3 to Day -1 at 0.5 mg/kg IV on Day -3; 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.; Other Names: Thymoglobulin Antithymocyte Globulin ; Drug: Filgrastim; Subcutaneous injection daily, starting 1 week after Stem Cell Transplant.; Other Names: G-CSF Granulocyte colony-stimulating factor GCSF

Outcome Measures

Primary Outcome Measures

1. Treatment Related Mortality [First 30 Days]

   Number of participants with treatment related mortality (death) within the first 30 days following transplantation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors.

2. Patient has not been administered intensive systemic chemotherapeutic drugs within 21 days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec, alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment.

3. No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy.

4. age </= 60

5. A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current standard for the BMT program).

6. ZUBROD performance status <2

7. Life expectancy is not severely limited by concomitant illness.

8. Left ventricular ejection fraction >/=45% No uncontrolled arrhythmias or symptomatic cardiac disease.

9. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine

10. Serum creatinine </= 1.5 mg%.

11. Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror to determining study eligibility.

12. Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).

13. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Exclusion Criteria:

1. Effusion or ascites estimated to be >1L prior to drainage.

2. HIV-positive.

3. Hepatitis C or HBsAg positive

4. Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of >/= 12 mg/kg given by mouth or >/= 10 mg/kg IV, or a total-body irradiation-based program.

5. Active or prior Central Nervous System (CNS) leukemia

6. Biphenotypic acute leukemia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Richard E. Champlin, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00469014
• Other Study ID Numbers: 2006-0200
• First Posted: May 4, 2007
• Last Update Posted: Jan 26, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by M.D. Anderson Cancer Center: Acute Myeloid Leukemia; AML; Myelodysplastic Syndrome; MDS; Chronic Myeloid Leukemia; CML; Busulfan; Busulfex; Myleran; Fludarabine; Fludara; Fludarabine Phosphate; Clofarabine; Clofarex; Clolar; Allogeneic stem cell transplantation; ASCT; Stem Cell; Gleevec; Imatinib Mesylate
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Syndrome; Vidarabine; Fludarabine; Fludarabine phosphate; Busulfan; Clofarabine; Thymoglobulin; Antilymphocyte Serum; Lenograstim

Study Results

Participant Flow

Recruitment Details	Recruitment Details: September 25, 2006 to March 30, 2011. All participants were recruited at the University of Texas (UT) MD Anderson Cancer Center.
Pre-assignment Detail	Of the 72 enrolled participants, one participant was not eligible and not treated. In the initial phase, the first 20 participants were fairly randomized to each of the 4 treatment arms. The rest of the participants were adaptively randomized among the arms in period 2.

Arm/Group Title	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine	Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine	Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine	Arm 4: Busulfan + Clofarabine
Arm/Group Description	4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Period Title: Initial Phase Randomization
STARTED	5	4	5	6
COMPLETED	4	3	4	5
NOT COMPLETED	1	1	1	1
Period Title: Initial Phase Randomization
STARTED	13	3	24	11
COMPLETED	12	2	23	10
NOT COMPLETED	1	1	1	1

Baseline Characteristics

Arm/Group Title	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine	Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine	Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine	Arm 4: Busulfan + Clofarabine	Total
Arm/Group Description	4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	Total of all reporting groups
Overall Participants	18	7	29	17	71
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	33	54	38	47	46
Sex: Female, Male (Count of Participants)
Female	10 55.6%	1 14.3%	14 48.3%	6 35.3%	31 43.7%
Male	8 44.4%	6 85.7%	15 51.7%	11 64.7%	40 56.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 38.9%	1 14.3%	4 13.8%	3 17.6%	15 21.1%
Not Hispanic or Latino	10 55.6%	6 85.7%	24 82.8%	14 82.4%	54 76.1%
Unknown or Not Reported	1 5.6%	0 0%	1 3.4%	0 0%	2 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 5.6%	0 0%	0 0%	0 0%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 5.6%	1 14.3%	2 6.9%	0 0%	4 5.6%
White	15 83.3%	6 85.7%	26 89.7%	17 100%	64 90.1%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5.6%	0 0%	1 3.4%	0 0%	2 2.8%
Region of Enrollment (participants) [Number]
United States	18 100%	7 100%	29 100%	17 100%	71 100%

Outcome Measures

1. Primary Outcome

Title	Treatment Related Mortality
Description	Number of participants with treatment related mortality (death) within the first 30 days following transplantation.
Time Frame	First 30 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine	Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine	Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine	Arm 4: Busulfan + Clofarabine
Arm/Group Description	4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.	4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
Measure Participants	13	3	24	11
Number [participants]	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Enrollment period defined as BMT Day -9 through BMT Day +28, post study surveillance defined as BMT Day +29 through +100. Thereafter, participant status/survival data collected quarterly as available. End of active treatment is day of stem cell infusion.
Arm/Group Title	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine		Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine		Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine		Arm 4: Busulfan + Clofarabine
Arm/Group Description	4-day Treatment Period Day -6 to Day -2: Busulfan 30 mg/m^2 intravenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily; Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.		4-day Treatment Period Day -6 to Day -2: Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.		4-day Treatment Period Day -6 to Day -2: Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.		4-day Treatment Period Day -6 to Day -2: Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily. Thymoglobulin Day -3 to Day -1, and Stem Cell Infusion Day 0.
All Cause Mortality
	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine		Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine		Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine		Arm 4: Busulfan + Clofarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/71 (2.8%)		1/71 (1.4%)		4/71 (5.6%)		1/71 (1.4%)
Serious Adverse Events
	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine		Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine		Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine		Arm 4: Busulfan + Clofarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/71 (21.1%)		6/71 (8.5%)		27/71 (38%)		15/71 (21.1%)
Blood and lymphatic system disorders
Bleeding (no GI no PUL)	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Febrile neutropenia	8/71 (11.3%)		3/71 (4.2%)		15/71 (21.1%)		8/71 (11.3%)
HSCT related microangiopathy (TA-TMA)	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Low granulocyte	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Cardiac disorders
Chest pain	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dysrhythmia	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Ejection fraction decreased	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Myocardial infarction	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Pericarditis	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Ear and labyrinth disorders
Tinnitus	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Eye disorders
Blurred vision	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dry eye	1/71 (1.4%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Ocular GvHD	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Gastrointestinal disorders
Abdominal pain	0/71 (0%)		0/71 (0%)		3/71 (4.2%)		0/71 (0%)
Diarrhea	1/71 (1.4%)		0/71 (0%)		3/71 (4.2%)		0/71 (0%)
Gastrointestinal bleeding	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
GI FIS	0/71 (0%)		1/71 (1.4%)		0/71 (0%)		0/71 (0%)
GI OTH	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Nausea	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Oral GvHD	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Oral mucositis	1/71 (1.4%)		0/71 (0%)		6/71 (8.5%)		1/71 (1.4%)
General disorders
AL OTH	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Fatigue	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Fever	0/71 (0%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Fluid overload	0/71 (0%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Hepatobiliary disorders
HP OTH	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
VOD	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Immune system disorders
Allergic reaction	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Infections and infestations
Bacterial	4/71 (5.6%)		3/71 (4.2%)		13/71 (18.3%)		6/71 (8.5%)
Fungal	0/71 (0%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Parasite	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Viral	4/71 (5.6%)		0/71 (0%)		4/71 (5.6%)		1/71 (1.4%)
Injury, poisoning and procedural complications
Infusion related reaction	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Investigations
ALK increased	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
ALT increased	7/71 (9.9%)		0/71 (0%)		6/71 (8.5%)		5/71 (7%)
AST increased	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Creatinine increased	1/71 (1.4%)		1/71 (1.4%)		0/71 (0%)		0/71 (0%)
Low platelet	4/71 (5.6%)		0/71 (0%)		4/71 (5.6%)		0/71 (0%)
T bilirubin increased	2/71 (2.8%)		1/71 (1.4%)		3/71 (4.2%)		0/71 (0%)
Metabolism and nutrition disorders
Anorexia	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Hyperglycemia	2/71 (2.8%)		1/71 (1.4%)		2/71 (2.8%)		0/71 (0%)
Hypomagnesemia	0/71 (0%)		0/71 (0%)		0/71 (0%)		3/71 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Bone pain	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Fasciitis	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Generalized muscle weakness	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Nervous system disorders
Dizziness	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Encephalopathy	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Headache	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
NE COR	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
NE PAI	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Peripheral neuropathy	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Somnolence	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Psychiatric disorders
Anxiety	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Confusion	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Hallucination	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Psychosis	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Renal and urinary disorders
Hemorrhagic Cystitis	1/71 (1.4%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Reproductive system and breast disorders
Vaginal dryness	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Respiratory, thoracic and mediastinal disorders
BOOP	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Broncholitis obliterans	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
DAH	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dyspnea	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Pneumonitis	1/71 (1.4%)		0/71 (0%)		3/71 (4.2%)		1/71 (1.4%)
Skin and subcutaneous tissue disorders
Chronic GVHD	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dry skin	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Rash	3/71 (4.2%)		1/71 (1.4%)		3/71 (4.2%)		3/71 (4.2%)
Skin discoloration	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Vascular disorders
Hypertension	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Hypotension	2/71 (2.8%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Thromboembolic event	1/71 (1.4%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine		Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine		Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine		Arm 4: Busulfan + Clofarabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/72 (25%)		7/72 (9.7%)		29/72 (40.3%)		16/72 (22.2%)
Blood and lymphatic system disorders
Bleeding (no GI no PUL)	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Febrile neutropenia	1/71 (1.4%)		3/71 (4.2%)		0/71 (0%)		0/71 (0%)
HSCT related microangiopathy (TA-TMA)	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Low granulocyte	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Cardiac disorders
Chest pain	0/71 (0%)		1/71 (1.4%)		0/71 (0%)		0/71 (0%)
Dysrhythmia	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Ejection fraction decreased	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Myocardial infarction	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Pericarditis	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Ear and labyrinth disorders
Tinnitus	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Eye disorders
Blurred vision	1/71 (1.4%)		1/71 (1.4%)		0/71 (0%)		0/71 (0%)
Dry eye	4/71 (5.6%)		0/71 (0%)		0/71 (0%)		7/71 (9.9%)
Ocular GvHD	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Gastrointestinal disorders
Abdominal pain	3/71 (4.2%)		3/71 (4.2%)		1/71 (1.4%)		1/71 (1.4%)
Diarrhea	8/71 (11.3%)		5/71 (7%)		0/71 (0%)		7/71 (9.9%)
Gastrointestinal bleeding	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
GI FIS	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
GI OTH	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Nausea	18/71 (25.4%)		6/71 (8.5%)		27/71 (38%)		16/71 (22.5%)
Oral GvHD	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Oral mucositis	17/71 (23.9%)		6/71 (8.5%)		23/71 (32.4%)		14/71 (19.7%)
General disorders
AL OTH	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Fatigue	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Fever	7/71 (9.9%)		3/71 (4.2%)		12/71 (16.9%)		7/71 (9.9%)
Fluid overload	2/71 (2.8%)		0/71 (0%)		0/71 (0%)		3/71 (4.2%)
Hepatobiliary disorders
HP OTH	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
VOD	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Immune system disorders
Allergic reaction	0/71 (0%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Infections and infestations
Bacterial	3/71 (4.2%)		2/71 (2.8%)		5/71 (7%)		2/71 (2.8%)
Fungal	3/71 (4.2%)		0/71 (0%)		4/71 (5.6%)		2/71 (2.8%)
Parasite	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Viral	6/71 (8.5%)		3/71 (4.2%)		17/71 (23.9%)		6/71 (8.5%)
Injury, poisoning and procedural complications
Infusion related reaction	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Investigations
ALK increased	3/71 (4.2%)		0/71 (0%)		5/71 (7%)		3/71 (4.2%)
ALT increased	10/71 (14.1%)		1/71 (1.4%)		10/71 (14.1%)		5/71 (7%)
AST increased	0/71 (0%)		0/71 (0%)		2/71 (2.8%)		0/71 (0%)
Creatinine increased	2/71 (2.8%)		2/71 (2.8%)		0/71 (0%)		4/71 (5.6%)
Low platelet	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
T bilirubin increased	3/71 (4.2%)		0/71 (0%)		4/71 (5.6%)		5/71 (7%)
Metabolism and nutrition disorders
Anorexia	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Hyperglycemia	1/71 (1.4%)		0/71 (0%)		1/71 (1.4%)		3/71 (4.2%)
Hypomagnesemia	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Bone pain	1/71 (1.4%)		1/71 (1.4%)		0/71 (0%)		1/71 (1.4%)
Fasciitis	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Generalized muscle weakness	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Nervous system disorders
Dizziness	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Encephalopathy	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Headache	6/71 (8.5%)		2/71 (2.8%)		7/71 (9.9%)		5/71 (7%)
NE COR	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
NE PAI	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Peripheral neuropathy	2/71 (2.8%)		1/71 (1.4%)		1/71 (1.4%)		0/71 (0%)
Somnolence	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Psychiatric disorders
Anxiety	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)
Confusion	1/71 (1.4%)		1/71 (1.4%)		0/71 (0%)		0/71 (0%)
Hallucination	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Psychosis	0/71 (0%)		0/71 (0%)		4/71 (5.6%)		0/71 (0%)
Renal and urinary disorders
Hemorrhagic Cystitis	3/71 (4.2%)		2/71 (2.8%)		7/71 (9.9%)		5/71 (7%)
Reproductive system and breast disorders
Vaginal dryness	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		1/71 (1.4%)
Respiratory, thoracic and mediastinal disorders
BOOP	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Broncholitis obliterans	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
DAH	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dyspnea	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Pneumonitis	1/71 (1.4%)		0/71 (0%)		4/71 (5.6%)		0/71 (0%)
Skin and subcutaneous tissue disorders
Chronic GVHD	1/71 (1.4%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Dry skin	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Rash	15/71 (21.1%)		4/71 (5.6%)		19/71 (26.8%)		11/71 (15.5%)
Skin discoloration	0/71 (0%)		0/71 (0%)		0/71 (0%)		1/71 (1.4%)
Vascular disorders
Hypertension	1/71 (1.4%)		2/71 (2.8%)		2/71 (2.8%)		0/71 (0%)
Hypotension	0/71 (0%)		0/71 (0%)		0/71 (0%)		0/71 (0%)
Thromboembolic event	0/71 (0%)		0/71 (0%)		1/71 (1.4%)		0/71 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.