Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML (OPAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00780598
Recruitment Status : Completed
First Posted : October 27, 2008
Last Update Posted : June 28, 2012
Quintiles, Inc.
Information provided by (Responsible Party):
Chroma Therapeutics

October 24, 2008
October 27, 2008
June 28, 2012
October 2009
March 2011   (Final data collection date for primary outcome measure)
The primary objective of the study is to evaluate the efficacy of tosedostat in elderly subjects with treatment refractory or relapsed AML by measuring CR and CRp. [ Time Frame: Months 1, 2, 3 & 6 ]
Same as current
Complete list of historical versions of study NCT00780598 on Archive Site
  • To evaluate the safety and tolerability of tosedostat in elderly subjects with treatment refractory or relapsed AML [ Time Frame: Screening, Days 1, 2, 8, 15, 29, monthly thereafter + unschedulded visits when deemed necessary ]
  • To evaluate the efficacy of tosedostat in elderly subjects with treatment refractory or relapsed AML, as determined by measures other than CR and CRp for the type and duration of response [ Time Frame: Months 1, 2, 3 & 6 ]
Same as current
Not Provided
Not Provided
Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML
The OPAL Study: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of Tosedostat (CHR-2797) in Elderly Subjects With Treatment Refractory or Relapsed Acute Myeloid Leukemia
The purpose of this study is to evaluate the efficacy and safety of tosedostat in elderly patients suffering from refractory or relapsed AML.

There is an urgent need for novel compounds and treatment strategies for elderly patients with AML, particularly those with refractory or relapsed disease for whom there are few effective treatment options. Treatment options for elderly patients are further limited by co-morbidity and tolerability constraints.

Tosedostat is a new aminopeptidase inhibitor, which in preclinical experiments has shown potent activity in both in vitro and in vivo cancer models as a single agent. In early clinical studies particularly good results have been observed in refractory and relapsed AML in older patients and these observations form the basis for the current study.

This multi-center, open label phase II study will enrol approximately 70 subjects in Part A and 130 subjects in Part B.

Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Acute Myeloid Leukemia
  • AML
Drug: Tosedostat

In Part A, approximately 70 subjects will be randomized to one of 2 dose regimens of tosedostat which will be administered orally, once daily. The dose regimens of tosedostat will be:

  • 120 mg for 6 months once daily, OR
  • 240 mg (induction dose) once daily for 2 months, followed by 120 mg(maintenance dose) for 4 months

In Part B a further 130 subjects will receive the dose regimen of tosedostat identified in Part A as being appropriate, based on the interim analysis during Part A.

Other Names:
  • - CHR-2797
  • - Aminopeptidase inhibitor
Experimental: Tosedostat
oral, once daily administration of tosedostat to evaluate its efficacy, safety and tolerability
Intervention: Drug: Tosedostat

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
March 2011
March 2011   (Final data collection date for primary outcome measure)


  1. Signed, informed consent prior to any study specific procedure
  2. Subjects with a confirmed diagnosis of AML according to WHO classification (excluding APL) who have had either a first CR lasting less than 12 months, or have not had a first CR and who will receive their first salvage therapy in this study [6]. For the purposes of this study, the following considerations apply:

    1. Subjects should have received only 1 induction course, but this may have consisted of more than one cycle of treatment, with different agents or doses in each cycle
    2. Induction courses should normally have consisted of agents and doses considered as standard of care for induction at the investigational site concerned
    3. Subjects may have received consolidation for any number of cycles. Consolidation will be considered as any regimens given while the subject was in remission
    4. Subjects who received hematopoietic stem cell transplant in first remission are eligible provided there has been no chemotherapy or other targeted therapies to treat a relapse, and there is no evidence of Graft Versus Host Disease (GVHD). Donor leukocyte infusion is allowed provided there is no evidence of hematologic relapse as defined by the International Working Group (IWG) [12]
  3. Subject's peripheral blast count does not exceed 30,000/microlitre before randomization into the study. Hydroxyurea treatment or leukapheresis may be used prior to or during the screening period to achieve this - see Section 6.7.2.
  4. Subject's life expectancy at randomization is judged to be at least 3 months
  5. Subjects should have recovered from the adverse effects of prior therapies to grade ≤1 (according to CTCAE v3) (excluding alopecia and any adverse effects that are expected to be chronic and stable)
  6. Subjects must have had a bone marrow aspiration performed within 28 days prior to randomization showing the subject has at least 5% blasts and is therefore neither in CR nor CRp. This may be done at the Screening Visit if appropriate and feasible
  7. Subjects must have adequate hepatic and renal function including the following:

    1. Total bilirubin ≤ 1.5 x upper limit of normal (in the absence of Gilbert's syndrome)
    2. AST and ALT ≤ 2.5 x upper limit of normal
    3. Serum creatinine ≤ 1.5 x upper limit of normal
  8. Age ≥ 60 years
  9. Performance status ≤ 2 (ECOG scale)
  10. Screening left ventricular ejection fraction (LVEF) ≥ 50%
  11. Subject is able to comply with all study procedures during the study including all visits and tests
  12. Male subjects with female partners of reproductive potential must use acceptable contraceptive methods for the duration of time on study and continue to do so for a further 3 months after the end of tosedostat treatment


  1. Subjects who have received prior therapy for first relapse or refractory disease (a second induction cycle within a single induction regimen is allowed as defined above in Inclusion criterion 2)
  2. Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of any other investigational agents within 2 weeks prior to randomization (with the exception of hydroxyurea which can be used in certain circumstances. Section 6.7.2)
  3. Subjects with APL (FAB type M3) or CML in blast crisis
  4. Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
  5. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
  6. Significant* cardiovascular disease defined as:

    1. Congestive heart failure NYHA class 4
    2. Unstable angina pectoris
    3. History of myocardial infarction within 6 months prior to study entry
    4. Presence of clinically significant valvular heart disease
    5. Uncontrolled or clinically significant ventricular arrhythmia
    6. Presence of clinically significant conduction defect on screening ECG
    7. Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
    8. Clinically significant atrial fibrillation *Grade 3/4 in the CTCAE v3 grading would generally be considered clinically significant, although this remains a judgment for the Investigator to make.
  7. Gastrointestinal disorders that may interfere with absorption of drug
  8. Active serious infection or sepsis at randomization
  9. Clinically significant interstitial lung disease
Sexes Eligible for Study: All
60 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Canada,   Netherlands,   United States
Not Provided
Not Provided
Chroma Therapeutics
Chroma Therapeutics
Quintiles, Inc.
Principal Investigator: Jorge E Cortes, MD M.D. Anderson Cancer Center
Principal Investigator: Karen Yee, MD Princess Margaret Hospital, Canada
Principal Investigator: Eric Feldman, MD Weill Cornell Medical College - New York Presbyterian Hospital
Principal Investigator: David Rizzieri, MD Duke University
Principal Investigator: Joseph Jurcic, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Richard Larson, MD University of Chicago
Principal Investigator: Hanna J Khoury, MD Emory University Clinic
Principal Investigator: Harry Erba, MD University of Michigan
Principal Investigator: Samir Parekh, MD Montefiore Medical Center
Principal Investigator: Aarthi Shenoy, MD Washington Hospital Center
Principal Investigator: Anjali Advani, MD Taussig Cancer Institute
Principal Investigator: Shambavi Richard, MD Stony Brook University Medical Center
Principal Investigator: Steven Allen, MD Monter Cancer Center
Principal Investigator: Ehab Attalah, MD Froedtert Hospital
Principal Investigator: John Storring, MD Royal Victoria Hospital
Principal Investigator: Gerrit J Ossenkoppele, MD VUMC
Principal Investigator: Pieter Sonneveld, MD Erasmus MC
Principal Investigator: Gary Schiller, MD UCLA Division of Hematology/oncology, Los Angeles
Principal Investigator: Peter Westervelt, MD Washington University School of Medicine
Principal Investigator: Julio Hajdenberg, MD MD Anderson Cancer centre, Orlando, FL
Principal Investigator: Stuart Goldberg, MD John Theurer Cancer Center, Hackensack NJ
Chroma Therapeutics
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP