Clofarabine Bone Marrow Cytoreduction

Clofarabine Bone Marrow Cytoreduction : Feasibility of Induction as a Bridge to Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Acute Leukemias, Myelodysplastic Syndromes, and Advanced Myeloproliferative Diseases.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00724009

Enrollment

Registered

2008-07-29

Start date

2007-12-31

Completion date

2012-09-30

Last updated

2014-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Brief summary

For relapsed and refractory leukemia patients induction chemotherapy prior to initiating a conditioning regimen will decrease residual leukemia (as measured by bone marrow leukemia blast percentage) at the time of HCT. This should lead to reduced relapse while still maintaining low transplant related mortality.

Detailed description

Screening will be done prior to enrollment in the study. The following will be done as part of the screening process: * Medical history review * Physical exam * Measurement of vital Signs * Blood tests (approximately 6 teaspoons of blood) will be done to see if the liver and kidneys are healthy, HIV (the virus that causes AIDS) test for this study and pregnancy test. * Urine test * Bone marrow biopsy and aspirate If the patient is ineligible or does not have a donor for Allogeneic Stem Cell transplantation, you will not be able to participate in this clinical trial. After results of these tests are obtained, your doctor will decide whether you can participate in this study. Study procedures: The study drug will be given for 5 days. Days 1 through 5: The patient will receive dexamethasone 1.5 hours prior to the administration of Clofarabine as part of standard care for subjects receiving Clofarabine. The patient will receive an intravenous (IV) injection (into the vein) of Clofarabine each day for 5 days. This injection is given in the hospital and will be given over approximately 60 minutes each day. The actual dose of Clofarabine is based on the weight and height of the subject. The patient will have the following tests done to see the effects of the study drug: Each day of Clofarabine administration, on day 12 and then each day until stem cell transplantation: * Physical exam * Vital signs * Blood tests. About 3-4 teaspoons will be taken each time. Day 12 after Clofarabine administration and then as outlined for stem cell transplantation: • Bone marrow biopsy and aspirate. After Clofarabine administration, there will be short resting period of 7-14 days. After the resting period, the patient will start receiving conditioning chemotherapy regimen (other standard of care drugs to better prepare your body for the stem cell transplant). This regimen will begin 15-21 days after they first received Clofarabine, and consists of additional treatment (chemotherapy and/or radiation). The type of treatment(s) the patient will receive for conditioning is dependent on the type of disease. In addition, this treatment will be decided by your doctor and is independent of this research. The duration of the conditioning period is variable and may take between 5-8 days. Stem cells are usually given one day after the completion of this regimen, which will be between 21 and 30 days after the patient has first received Clofarabine. Follow-up Subjects who have a response and proceed with stem cell transplant will be followed weekly for the first three months and then every month for six months, then every two months for 12 months, then every three months for 18 months. The stem cell transplant will be done 21-30 days after first receiving Clofarabine. Subjects who do not go on to stem cell transplant will be followed for 3 months following administration of Clofarabine. At these visits, the following will be done: * A physical exam * Medical history * Blood tests (about 3 teaspoons blood will be taken) performed. End of study At this time, the following tests will be done: * Physical exam * Blood tests * Bone marrow biopsy

Interventions

DRUGClofarabine

Clofarabine for injection should be diluted with 0.9% sodium chloride injection USP or European Pharmacopeia (EP) normal saline (NS) or 5% dextrose injection (D5W) USP or EP prior to IV infusion. The resulting admixture may be stored at room temperature, but must be used within 24 hours of preparation. Clofarabine should be diluted with NS or D5W prior to administering by IV infusion. The dosage is based on the patient's body surface area (BSA), calculated using the actual height and weight before the start of each cycle. To prevent drug incompatibilities, no other medications should be administered through the same IV line.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. * Adequate hepatobiliary function as indicated by the following laboratory values: * SGOT/SGPT \<=2.5 x upper limit of normal * Alkaline phosphatase \<=2.5 x upper limit of normal * Serum bilirubin \< 1.5 mg/dl * Adequate renal function as indicated by the following laboratory values: * Creatinine Clearance \>50 ml/min * Age \>/=18 years * Zebroid performance status \</= 2 (See Appendix A) * Life expectancy is not severely limited by concomitant illness (i.e. \< 3months life expectancy from non-leukemic conditions). * No evidence of chronic active hepatitis or cirrhosis. * HIV-negative * Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. * Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.

Exclusion criteria

* Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. * Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute non-hematologic toxicities from any previous . * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Pregnant or lactating patients. * Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Design outcomes

Primary

Measure	Time frame	Description
Cytoreductive Response	Day 12	Percent of patients achieving cytoreductive response of marrow cellularity \<20% and blasts \< 10%

Secondary

Measure	Time frame	Description
Number of Participants With Hepatic (Total Bilirubin) Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of Participants With Hepatic (SGOT) Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of Participants With Cardiac Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of Participants With Renal Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Number of Participants Infection Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Leukemia Free Survival	2 years	Time to event analysis used the day of transplant as day 0.
Number of Participants With Skin Adverse Events	Day 12	Treatment-related toxicity was calculated according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Clofarabine Clofarabine 30 mg/m2/day IV infusion over one hour for 5 consecutive days Clofarabine: Clofarabine for injection should be diluted with 0.9% sodium chloride injection USP or European Pharmacopeia (EP) normal saline (NS) or 5% dextrose injection (D5W) USP or EP prior to IV infusion. The resulting admixture may be stored at room temperature, but must be used within 24 hours of preparation. Clofarabine should be diluted with NS or D5W prior to administering by IV infusion. The dosage is based on the patient's body surface area (BSA), calculated using the actual height and weight before the start of each cycle. To prevent drug incompatibilities, no other medications should be administered through the same IV line.	29
Total	29

Arm

Count

Clofarabine

Clofarabine 30 mg/m2/day IV infusion over one hour for 5 consecutive days Clofarabine: Clofarabine for injection should be diluted with 0.9% sodium chloride injection USP or European Pharmacopeia (EP) normal saline (NS) or 5% dextrose injection (D5W) USP or EP prior to IV infusion. The resulting admixture may be stored at room temperature, but must be used within 24 hours of preparation. Clofarabine should be diluted with NS or D5W prior to administering by IV infusion. The dosage is based on the patient's body surface area (BSA), calculated using the actual height and weight before the start of each cycle. To prevent drug incompatibilities, no other medications should be administered through the same IV line.

Total

Baseline characteristics

Characteristic	Clofarabine
Age, Continuous	51 years
Sex: Female, Male Female	13 Participants
Sex: Female, Male Male	16 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	26 / 29
serious Total, serious adverse events	22 / 29

Outcome results

Primary

Cytoreductive Response

Percent of patients achieving cytoreductive response of marrow cellularity \<20% and blasts \< 10%

Time frame: Day 12

Arm	Measure	Value (NUMBER)
Clofarabine	Cytoreductive Response	52 percentage of participants

Secondary

Leukemia Free Survival

Time to event analysis used the day of transplant as day 0.

Time frame: 2 years

Population: One patient with refractory AML underwent conditioning but died 1 day before stem cell infusion due to sepsis (grade 5 infection)

Arm	Measure	Value (MEDIAN)
Clofarabine	Leukemia Free Survival	211 days

Secondary