Trial Outcomes & Findings for Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen (NCT NCT00556452)

Last Updated: 2017-12-05

Results Overview

The incidence of non-hematological toxicities (Common Terminology Criteria for Adverse Events (CTCAE) 3.0) from initiation of conditioning to Day + 30 or toxicities after day +30, possibly, probably or definitely related to conditioning for all patients treated with Clofarabine (independent of dose level).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

46 participants

Primary outcome timeframe

two years

Results posted on

2017-12-05

Participant Flow

Patients with relapsed or refractory hematologic malignancies not in remission received unmanipulated HSCT with CloBu4 conditioning from October 2007 to November 2009 at the University of Michigan. Patients received a clofarabine dose of 20mg/m\^2, 30 mg/m\^2 or 40 mg/m\^2.

Participant milestones

Participant milestones
Measure	Clo/BU4 20mg/m^2 Clofarabine/Busulfan x 4 : Clofarabine IV 20 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.	Clo/BU4 30mg/m^2 Clofarabine/Busulfan x 4 : Clofarabine IV 30 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.	Clo/BU4 40mg/m^2 Clofarabine/Busulfan x 4 : Clofarabine IV 40 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.
Overall Study STARTED	6	21	19
Overall Study COMPLETED	6	21	19
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Stem Cell Transplantation for Hematologic Malignancies Using Clofarabine and Busulfan Regimen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clo/BU4 20mg/m^2 n=6 Participants Clofarabine/Busulfan x 4 : Clofarabine IV 20 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.	Clo/BU4 30mg/m^2 n=21 Participants Clofarabine/Busulfan x 4 : Clofarabine IV 30 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.	Clo/BU4 40mg/m^2 n=19 Participants Clofarabine/Busulfan x 4 : Clofarabine IV 40 mg/m\^2/day x 5 days Busulfan IV 3.2 mg/kg daily x 4 days Peripheral blood stem cell transplant : Peripheral blood stem cell transplant, after pre-conditioning drug treatment.	Total n=46 Participants Total of all reporting groups
Age, Continuous	48.5 years n=93 Participants	54 years n=4 Participants	51 years n=27 Participants	53 years n=483 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	9 Participants n=4 Participants	11 Participants n=27 Participants	22 Participants n=483 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	12 Participants n=4 Participants	8 Participants n=27 Participants	24 Participants n=483 Participants
Region of Enrollment United States	6 participants n=93 Participants	21 participants n=4 Participants	19 participants n=27 Participants	46 participants n=483 Participants
Disease Acute Myeloid Leukemia (AML)	4 participants n=93 Participants	13 participants n=4 Participants	14 participants n=27 Participants	31 participants n=483 Participants
Disease Chronic Myeloid Leukemia (CML)	1 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	2 participants n=483 Participants
Disease Acute Lymphoblastic Leukemia (ALL)	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants	4 participants n=483 Participants
Disease Chronic Lymphocytic Leukemia (CLL)	0 participants n=93 Participants	3 participants n=4 Participants	1 participants n=27 Participants	4 participants n=483 Participants
Disease Non-Hodgkin Lymphoma (NHL)	0 participants n=93 Participants	2 participants n=4 Participants	1 participants n=27 Participants	3 participants n=483 Participants
Disease Myelodysplastic Syndromes (MDS)	0 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants	1 participants n=483 Participants
Disease Multiple Myeloma (MM)	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants

PRIMARY outcome

Timeframe: two years

Outcome measures

Outcome measures
Measure	Clo/Bu4 n=46 Participants Experimental: Clo/BU4
Regimen Related Toxicities Liver	56 toxicities
Regimen Related Toxicities Gastrointestinal	70 toxicities
Regimen Related Toxicities Genito-Urinary	4 toxicities
Regimen Related Toxicities Cardiopulmonary	10 toxicities
Regimen Related Toxicities Neurologic	8 toxicities
Regimen Related Toxicities Skin	11 toxicities
Regimen Related Toxicities Other	3 toxicities

PRIMARY outcome

Timeframe: 1 year

Population: Patients with Acute Myeloid Leukemia (AML)

Percent Overall Survival (OS) for at one year for subjects with Acute Myeloid Leukemia (AML).

Outcome measures

Outcome measures
Measure	Clo/Bu4 n=31 Participants Experimental: Clo/BU4
One-year Overall Survival Rate for AML	48 percent overall survival Interval 34.0 to 70.0

SECONDARY outcome

Timeframe: 2 years

Percent Overall Survival (OS) at two years for all patients.

Outcome measures

Outcome measures
Measure	Clo/Bu4 n=46 Participants Experimental: Clo/BU4
Two-year Overall Survival for All Cases.	28 percent overall survival Interval 17.0 to 45.0

SECONDARY outcome

Timeframe: five years

The number of patients alive at 5 years

Outcome measures

Outcome measures
Measure	Clo/Bu4 n=46 Participants Experimental: Clo/BU4
Five Year Overall Survival for All Cases	6 Participants

Adverse Events

Clo/Bu4

Serious events: 23 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Clo/Bu4 n=46 participants at risk
Gastrointestinal disorders Ascites	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Diarrhea	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Respiratory, thoracic and mediastinal disorders Hypoxia/Dyspnea	6.5% 3/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
General disorders Fever	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Musculoskeletal and connective tissue disorders Bone Pain	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Vascular disorders Vascular Access Complication	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Musculoskeletal and connective tissue disorders Back Pain	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Cardiac disorders Atrial Fibrilation	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Vascular disorders Bladder Hemmorhage	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Blood and lymphatic system disorders Blood Disorder	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
General disorders Death	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Investigations Disease Progression	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Nervous system disorders Dizziness	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Esophagitis	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Immune system disorders Graft Versus Host Disease	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Infections and infestations Infection	15.2% 7/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Musculoskeletal and connective tissue disorders Muscle Weakness	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Vascular disorders Portal Hypertension	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Infections and infestations Sepsis	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.

Other adverse events

Other adverse events
Measure	Clo/Bu4 n=46 participants at risk
Hepatobiliary disorders Transaminitis*	93.5% 43/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Hepatobiliary disorders Hyperbilirubiniemia	17.4% 8/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Mucositis	67.4% 31/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Nausea/Vomiting	54.3% 25/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Diarrhea	21.7% 10/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Abdominal Pain	10.9% 5/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Renal and urinary disorders Creatinine elevation	6.5% 3/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Nervous system disorders Headache	8.7% 4/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Nervous system disorders Confusion	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Skin and subcutaneous tissue disorders Hand-foot syndrome	19.6% 9/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Skin and subcutaneous tissue disorders Rash	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
General disorders Hypotention	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Vascular disorders Veno-Occlusive Disease	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Gastrointestinal disorders Ascites	6.5% 3/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Cardiac disorders Hypertension	6.5% 3/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Renal and urinary disorders Hemorragic Cystitis	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Cardiac disorders Arrythmia	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
General disorders Hypersensitivity	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Respiratory, thoracic and mediastinal disorders Hypoxia	13.0% 6/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Nervous system disorders Syncope	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Musculoskeletal and connective tissue disorders Fracture	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Blood and lymphatic system disorders Febrile Neutropenia	45.7% 21/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Vascular disorders Deep Vein Thrombosis	4.3% 2/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Hepatobiliary disorders Cholycytitis	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Hepatobiliary disorders Cirrhosis	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.
Nervous system disorders Siezure	2.2% 1/46 • Adverse events occurring following study registration, but prior to beginning transplant therapy will not be reported. Post transplant, adverse events will be reported through day 100. Adverse events were analyzed for all patients that received Clofarabine, and not by Clofarabine dose received. All patients received the same study drug, Clofarabine.

Additional Information

Dr. John Magenau

University of Michigan Cancer Center

Phone: 734/936-8785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place