Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

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Brief Title

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.

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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.

Secondary Outcome

 Overall Survival

Condition

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Intervention

cediranib maleate

Study Arms / Comparison Groups

 Treatment (enzyme inhibitor therapy)
Description:  Patients receive oral cediranib maleate QD on days 1-28. Treatment repeats every 28 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

39

Start Date

May 2008

Completion Date

March 2012

Primary Completion Date

July 2011

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark Juckett, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00475150

Organization ID

NCI-2009-00129

Secondary IDs

NCI-2009-00129

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Mark Juckett, Principal Investigator, Mayo Clinic


Verification Date

December 2016