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Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Phase 2
40 Years
Open (Enrolling)
Acute Myeloid Leukemia

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Trial Information

Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

All patients are scheduled for at least one cycle of induction therapy with CLARA. CLARA
contains clofarabine 40 mg/m2 (1 hr infusion) days 1-5 followed 3 hours after the end of
infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-5. Patients with
moderate early response (reduced marrow blast count but ≥10% at day 15) or patients with
progressive disease during delayed hematologic recovery (beyond day 42) may receive
re-induction therapy similar to the first cycle induction therapy.

Study treatment comprises up to two cycles of induction therapy and one to two cycles of
consolidation chemotherapy for patients without a donor. Consolidation therapy is reduced by
25% and consists of clofarabine 40 mg/m2 (1 hr infusion) days 1-4 followed 3 hours after the
end of infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-4.

Patients for whom a donor can be identified may proceed to allogeneic HCT after CLARA I
adopting the concept of allogeneic HCT in aplasia. Patients for whom donor search is more
time consuming should proceed to allogeneic HCT once a donor has been identified.

Patients who have achieved a response after the last cycle of CLARA will receive clofarabine
as part of the conditioning regimen. Clofarabine and melphalan may only be given as
conditioning therapy to patients with HLA-compatible donors with a maximum of one mismatch
refering to the HLA-loci A, -B, -C and -DRB1. Conditioning therapy then contains clofarabine
30 mg/m2 (1 hr IV infusion) days -6 to -3 and melphalan 140 mg/m2 (1 hour IV infusion) on
day -2.

Inclusion Criteria:

- Diagnosis of AML according to WHO criteria.

- Untreated relapse or refractory disease after a minimum of one standard induction
therapy. Treatment of relapse with leukocyte-apheresis or up to 5 days with low dose
cytarabine or hydroxyurea is allowed.

- Refractory disease is defined as ≥5% blasts after the second cycle of induction
therapy or no reduction in marrow blasts at early treatment assessment (day +15)
after the first cycle of induction therapy.

- Relapse is defined as an increase in bone marrow blast count ≥5%, re-appearance
of blasts in the peripheral blood or extramedullary disease.

- Age above 40 years.

- Have adequate renal and hepatic functions as indicated by the following laboratory

- Serum creatinine <=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated
glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 (see reference

- Serum bilirubin <=1.5× upper limit of normal (ULN)

- Aspartate transaminase (AST)/alanine transaminase (ALT) <=2.5× ULN

- Alkaline phosphatase <=2.5× ULN

- Eligibility for intensive chemotherapy

- Patient needs to be capable to understand the clinical trial as an investigational
approach to bridge the time to potential allogeneic HCT, potential risks and benefits
of the study.

- Signed written informed consent.

- Female patients of childbearing potential must have a negative serum

- Male and female patients must use an effective contraceptive method during the study
and for a minimum of 6 months after study treatment.

Exclusion Criteria:

- For refractory disease, more than two prior induction chemotherapies or more than one
prior salvage chemotherapy containing high-dose cytarabine (cumulative dose of
cytarabine ≥ 5 g/m2).

- Second or higher relapse. Patients who received hypomethylating agents like
azacytidine or decitabine as a treatment of first relapse, respond and relapse later
on may be included.

- Acute promyelocytic leukemia with t(15;17)(q22;q12) molecular detection or

- Central nervous system involvement (i.e. WBC ≥ 5/µL in cerebrospinal fluid with
blasts present on cytospin).

- Prior allogeneic HCT

- Autologous transplantation within 100 days prior to start of study treatment

- Use of investigational agents or anticancer therapy within 10 days before study entry
with the exception of hydroxyurea or low-dose cytarabine.

- 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 transplantation.

- Patients with known refractoriness to platelet support.

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of treatment success

Outcome Description:

Treatment success is defined as a complete remission (CR, CRi or CRchim) at final response assessment after having completed the study treatment. CR and CRi are defined according to standard criteria (ELN). Complete remission by chimerism (CR chim) is defined as a >95% overall donor chimerism assessed by STR-PCR in bone marrow and absence of extramedullary disease together with an absolute neutrophil count >0.5 /nL (500/μL).

Outcome Time Frame:

To be evaluated 42 days after start of last cycle of chemotherapy containing clofarabine

Safety Issue:


Principal Investigator

Johannes Schetelig, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Universitätsklinikum Dresden, Med. Klinik und Poliklinik I, Study Alliance Leukemia


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

March 2011

Completion Date:

July 2013

Related Keywords:

  • Acute Myeloid Leukemia
  • acute myeloid leukemia
  • relapsed
  • refractory
  • Relapsed or refractory AML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid