Clinical trial NCT00475150: Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Official title: A Phase II Study of AZD2171 in the Treatment of Patients With Acute Leukemia and Myelodysplastic Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Untreated Adult Acute Myeloid Leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-05-17
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well cediranib maleate works in treating patients with relapsed, refractory, or untreated acute myeloid leukemia or high-risk myelodysplastic syndrome. Cediranib maleate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer.

Detailed description: PRIMARY OBJECTIVES:

I. Evaluate the objective response rate in patients with relapsed, refractory, or untreated acute myeloid leukemia or high-risk myelodysplastic syndromes treated with AZD2171 (cediranib maleate).

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. II. Determine the response duration, event-free survival, and overall survival of patients treated with this drug.

III. Determine the hematological response rate in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (acute myeloid leukemia vs myelodysplastic syndromes).

Patients receive oral cediranib maleate once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy at baseline and on day 28 for correlative studies. Samples are analyzed for circulating endothelial cells, VEGF receptor expression, and leukemic blasts via flow cytometry and microvessel density via histopathological techniques.

After completion of study treatment, patients are followed up at 3 months and then every 6 months for up to 2 years.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed acute myeloid leukemia (AML) ormyelodysplastic syndromes meeting 1 of the following criteria:

  * Relapsed AML meeting any of the following criteria:

    * Good-risk cytogenetics (inv\[16\], t\[8;21\], or t\[15;17\]) in second orgreater relapse

      * Patients with AML t(15;17) must have failed prior tretinoin and arsenic-containing regimens AND progressed orrelapsed within 12 months of therapy
    * In first or greater relapse
  * Resistant AML

    * Unable to achieve first complete remission after at least 2 inductionregimens
  * Untreated AML meeting any of the following criteria:

    * At least 60 years of age
    * Preceding MDS
  * MDS

    * International Prognosis Scoring System (IPSS) risk groupof intermediate-2 or higher
* Patients with relapsed disease after allogeneic hematopoietic stem cell transplantation (HSCT) must be off allimmunosuppressive medications for at least 30 days and have no symptoms orsigns of graft-vs-host disease
* No active CNS metastasis

  * Patients with clinical signs of CNS disease or a history of CNS diseasewithin the past 6 months are required to undergo lumbar puncture to excludeCNS involvement
* No symptomatic leukostasis or requirement for leukapheresis
* Not eligible for allogeneic HSCTAND no suitable donor at the time of study entry

  * Patients who areeligible for HSCT, informed of the option, and choose not to proceed to HSCTare allowed
* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* Bilirubin normal
* AST and/or ALT ≤ 2.5 times upper limit of normal
* Creatinine normal OR creatinine clearance ≥ 60 mL/min
* No proteinuria ≥ 1+ on 2 consecutive urinalysis taken ≥ 1 week apart
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No HIV positivity
* LVEF ≥ 45% by echocardiography
* Mean QTc ≤ 500 msec (with Bazett's correction)
* No other significant ECG abnormality
* No history of familial long QT syndrome
* No disseminated intravascular coagulation
* No history of allergic reactions attributed to compounds of similar chemical orbiological composition to AZD2171
* No concurrent uncontrolled illness, including, but not limited to, any of the following:

  * Hypertension
  * Thyroid disease
  * Ongoing or active infection
  * Symptomatic congestive heartfailure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * NYHA class III-IV heart disease

    * NYHA class II heart disease controlled with treatment allowed
  * Psychiatric illness or social situations that would limit study compliance
* See Disease Characteristics
* More than 4 weeks since prior chemotherapy (6 weeks fornitrosoureas or mitomycin C), radiotherapy, or major surgery and recovered

  * Hydroxyurea allowed to control peripheral blast count\> 20,000/mcL prior to study entry and during the first 3 days of study therapy
* More than 4 weeks since prior and no concurrent growth factor or other cytokine support
* At least 30 days since prior investigational agents or participation in aninvestigational trial
* No more than 3 prior courses of induction chemotherapy

  * Induction chemotherapyis defined as that intended to induce complete remission and given at a time thatthe patient has active disease
* No concurrent CYP interactive medications
* No other concurrent investigational agents
* No concurrent drugs or biologics with proarrhythmic potential
* Prior and concurrent hydroxyurea allowed to control peripheral blast count\> 20,000/mcL during the first 3 days of study therapy

Primary outcomes:
measure: The Number of Confirmed Disease Response: Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI). A Confirmed Response is Defined to be an Objective Status of CR, PR, or HI Noted on 2 Consecutive Evaluations.
timeFrame: At the end of cycles 1 and 3 and every 3 cycles thereafter up to 26 cycles
Secondary outcomes:
measure: Overall Survival
timeFrame: Every cycle during treatment and every 6 months for up to 2 years after completion of study treatment
measure: Progression-free Survival
timeFrame: Every 3 courses during treatment and then at 3 months and every 6 months for up to 2 years after completion of study treatment
measure: Duration of Response
timeFrame: Every 3 courses up to 26 courses
measure: The Number of Patients That Report Adverse Events Possibly, Probably, or Definitely Related to AZD2171.
timeFrame: Continuously during treatment up to 26 courses
Other outcomes:
Locations:
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Mark Juckett
role: PRINCIPAL_INVESTIGATOR
References: