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A Nonrandomized Dose-escalation Study of Clofarabine in Combination With Gemtuzumab Ozogamicin for Relapsed/Refractory Acute Myeloid Leukemia (AML) for Patients Less Than 60 Years-old

Phase 1
18 Years
60 Years
Open (Enrolling)

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Trial Information

A Nonrandomized Dose-escalation Study of Clofarabine in Combination With Gemtuzumab Ozogamicin for Relapsed/Refractory Acute Myeloid Leukemia (AML) for Patients Less Than 60 Years-old



- Identify the maximum tolerated dose and dose-limiting toxicities of clofarabine when
administered with gemtuzumab ozogamicin in patients with refractory acute myeloid
leukemia (AML) or with AML that has relapsed within 1 year after cytarabine-containing


- Estimate the rates of complete response and/or partial complete response with
incomplete platelet recovery in patients treated with this regimen.

- Estimate the duration of remission in patients treated with this regimen and not
proceeding to high-dose therapy and allogeneic stem cell transplantation.

- Estimate the frequency with which patients enrolled on this study proceed to allogeneic
or autologous blood or bone marrow stem cell transplantation.

OUTLINE: This is a dose-escalation study of clofarabine.

Patients receive induction therapy comprising clofarabine IV on days 1-5 and gemtuzumab
ozogamicin IV over 2 hours on days 1, 4, and 7 during course 1 only. Beginning in course 2,
after blood counts recover, patients receive consolidation therapy comprising clofarabine IV
on days 1-5. Consolidation treatment repeats upon blood count recovery for up to 2 courses
in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients in remission after consolidation therapy are
followed monthly for the first 6 months, and then every 3-4 months for 2 years.

Inclusion Criteria


- Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:

- Refractory disease, defined as persistent or progressive disease after ≥ 2
induction regimens, including ≥ 1 course of high-dose cytarabine (ARA-C)

- Relapsed disease that has recurred within 1 year of an ARA-C-containing
chemotherapy regimen

- No CNS disease requiring radiotherapy

- Patients with neurological symptoms must undergo a lumbar puncture and a CT scan
or MRI of the brain to exclude brain metastasis


- ECOG performance status 0-2

- Total bilirubin ≤ 2.0 times upper limit of normal (ULN)

- ALT and AST ≤ 2.0 times the ULN

- Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate > 60 mL/min

- INR ≤ 1.5 and aPTT within ULN

- Patients receiving anticoagulation therapy (e.g., warfarin or heparin) are
eligible provided anticoagulation therapy can be discontinued or changed to
parenteral medications while the platelet count is less than 50,000/mm³

- Negative pregnancy test

- Fertile patients must use effective contraception

- No concurrent active second primary malignancy (excluding superficial, non-invasive
skin cancers)

- No active bleeding diathesis, not including closely monitored therapeutic

- No cardiac disease, including any of the following:

- New York Heart Association class II-IV congestive heart failure

- Unstable angina (i.e., anginal symptoms at rest)

- New onset angina (i.e., began within the past 3 months)

- Myocardial infarction within the past 6 months

- No active clinically serious infection > grade 2

- No cerebrovascular accident, including transient ischemic attacks, within the past 6

- No pulmonary hemorrhage ≥ grade 2 within the past 4 weeks

- No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks

- No known HIV infection or chronic hepatitis B or C

- No serious non-healing wound or ulcer

- More than 4 weeks since prior significant traumatic injury

- No prior history of sinusoidal obstructive syndrome (veno-occlusive disease)


- More than 4 weeks since prior major surgery or open biopsy

- More than 100 days since any prior hematopoietic stem cell transplant

- No concurrent treatment with any other investigational agent for AML

- Intrathecal chemotherapy administration is allow for central nervous system
leukemic infiltration

- No prior allogeneic stem cell transplant within the past 100 days, with active
graft-versus-host disease (GVHD) of any grade, or exposure to immynosuppression for
GVHD or prophylaxis

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of clofarabine

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Thomas C. Shea, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:

LCCC 0708



Start Date:

November 2007

Completion Date:

September 2012

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570