Acute Myeloid LeukemiaPhase 2OPALNCT00780598
Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML
A Phase 2 study testing Tosedostat in people with Acute Myeloid Leukemia and AML, run by Chroma Therapeutics at 21 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of tosedostat in elderly patients suffering from refractory or relapsed AML. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, AML
- What is being tested?
- Tosedostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 21 sitesin 3 countries
- Study dates
- Oct 2009to Mar 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed, informed consent prior to any study specific procedure
- 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:
- 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
- Induction courses should normally have consisted of agents and doses considered as standard of care for induction at the investigational site concerned
- Subjects may have received consolidation for any number of cycles. Consolidation will be considered as any regimens given while the subject was in remission
- 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]
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- 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.
- Subject's life expectancy at randomization is judged to be at least 3 months
- 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)
- 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
- Subjects must have adequate hepatic and renal function including the following:
- Total bilirubin ≤ 1.5 x upper limit of normal (in the absence of Gilbert's syndrome)
- AST and ALT ≤ 2.5 x upper limit of normal
- Serum creatinine ≤ 1.5 x upper limit of normal
- Age ≥ 60 years
- Performance status ≤ 2 (ECOG scale)
- Screening left ventricular ejection fraction (LVEF) ≥ 50%
- Subject is able to comply with all study procedures during the study including all visits and tests
- 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
Who cannot join
- 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)
- 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)
- Subjects with APL (FAB type M3) or CML in blast crisis
- 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
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
- Significant* cardiovascular disease defined as:
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- Congestive heart failure NYHA class 4
- Unstable angina pectoris
- History of myocardial infarction within 6 months prior to study entry
- Presence of clinically significant valvular heart disease
- Uncontrolled or clinically significant ventricular arrhythmia
- Presence of clinically significant conduction defect on screening ECG
- Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
- 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.
- Gastrointestinal disorders that may interfere with absorption of drug
- Active serious infection or sepsis at randomization
- Clinically significant interstitial lung disease
Trial locations and contacts
21 sites in 3 countries.
21 sites in 3 countries
United States17 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109-0008
Emory University Clinic
Atlanta, Georgia, 30322
University of Chicago Medical Center
Chicago, Illinois, 60637
Taussig Cancer Institute
Cleveland, Ohio, 44195
Duke Univeristy Medical Center
Durham, North Carolina, 27710
John Theurer Cancer Center, Hackensack University Medical Center,
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
Monter Cancer Center
Lake Success, New York, 11042
UCLA School of Medicine
Los Angeles, California, 90095
Froedtert Hospital
Milwaukee, Wisconsin, 53226-3596
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10065
M.D. Anderson Cancer Center Orlando
Orlando, Florida, 32806
Washington University, Oncology/Bone Marrow Transplant
St Louis, Missouri, 63110
Stony Brook University Medical Center
Stony Brook, New York, 11794-7007
Montefiore Medical Center Weiler Division
The Bronx, New York, 10461
Washington Cancer Institute
Washington D.C., District of Columbia, 20010
Canada2 sites
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Princess Margaret Hopsital
Toronto, Ontario, M5G 2M9
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Acute Myeloid Leukemia, AML
- Being tested
- Tosedostat
- Keywords
- Acute Myeloid Leukemia, AML, Cancer, Hematological malignancies, Elderly, Refractory, Relapsed, Blood disorder
- Medical subject headings
- Leukemia, Myeloid, Acute, Neoplasms, Hematologic Neoplasms, Recurrence, Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TosedostatDrug
Also called - CHR-2797, - Aminopeptidase inhibitor
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.
| Study group | Role | What they receive |
|---|---|---|
| Tosedostat | Experimental | oral, once daily administration of tosedostat to evaluate its efficacy, safety and tolerability Receives: Drug: Tosedostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Months 1, 2, 3 & 6
Secondary outcomes (2)
To evaluate the safety and tolerability of tosedostat in elderly subjects with treatment refractory or relapsed AML
Measured: 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
Measured: Months 1, 2, 3 & 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2008 (estimated)
- Study startOct 2009
- Primary completionMar 2011
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chroma Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Responsible party
- Sponsor
- Investigators
- Jorge E Cortes, MD, Principal investigator, M.D. Anderson Cancer CenterKaren Yee, MD, Principal investigator, Princess Margaret Hospital, CanadaEric Feldman, MD, Principal investigator, Weill Cornell Medical College - New York Presbyterian HospitalDavid Rizzieri, MD, Principal investigator, Duke UniversityJoseph Jurcic, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterRichard Larson, MD, Principal investigator, University of ChicagoHanna J Khoury, MD, Principal investigator, Emory University ClinicHarry Erba, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00780598
- Sponsor's protocol ID
- CHR-2797-038
- Acronym
- OPAL
- Status last verified
- Mar 2012
- First submitted
- 24 Oct 2008
- Last updated
- 28 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Krige D, Needham LA, Bawden LJ, Flores N, Farmer H, Miles LE, Stone E, Callaghan J, Chandler S, Clark VL, Kirwin-Jones P, Legris V, Owen J, Patel T, Wood S, Box G, Laber D, Odedra R, Wright A, Wood LM, Eccles SA, Bone EA, Ayscough A, Drummond AH. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 2008 Aug 15;68(16):6669-79. doi: 10.1158/0008-5472.CAN-07-6627.
PubMed 18701491Estey E, Kornblau S, Pierce S, Kantarjian H, Beran M, Keating M. A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia. Blood. 1996 Jul 15;88(2):756. No abstract available.
PubMed 8695828Cortes J, Feldman E, Yee K, Rizzieri D, Advani AS, Charman A, Spruyt R, Toal M, Kantarjian H. Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. Lancet Oncol. 2013 Apr;14(4):354-62. doi: 10.1016/S1470-2045(13)70037-8. Epub 2013 Feb 28.
PubMed 23453583
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00780598
- Acronym / sponsor ID
- OPAL / CHR-2797-038
- Conditions
- Acute Myeloid Leukemia, AML
- Keywords
- Acute Myeloid Leukemia, AML, Cancer, Hematological malignancies, Elderly, Refractory, Relapsed, Blood disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Chroma TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Quintiles, Inc.
- Study start
- Oct 2009
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 27 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of tosedostat in elderly patients suffering from refractory or relapsed AML.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tosedostat | Experimental | Drug: Tosedostatoral, once daily administration of tosedostat to evaluate its efficacy, safety and tolerability |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed, informed consent prior to any study specific procedure
- 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:
- 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.
- Subject's life expectancy at randomization is judged to be at least 3 months
- 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)
Key exclusion criteria (17 listed)
- 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)
- 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)
- Subjects with APL (FAB type M3) or CML in blast crisis
- 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
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TosedostatAlso: - CHR-2797, - Aminopeptidase inhibitorIn 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. | Drug | Tosedostat |
Primary outcome
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
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2012.
- Background: PubMed 18701491Krige D, Needham LA, Bawden LJ, Flores N, Farmer H, Miles LE, Stone E, Callaghan J, Chandler S, Clark VL, Kirwin-Jones P, Legris V, Owen J, Patel T, Wood S, Box G, Laber D, Odedra R, Wright A, Wood LM, Eccles SA, Bone EA, Ayscough A, Drummond AH. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 2008 Aug 15;68(16):6669-79. doi: 10.1158/0008-5472.CAN-07-6627.
- Background: PubMed 8695828Estey E, Kornblau S, Pierce S, Kantarjian H, Beran M, Keating M. A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia. Blood. 1996 Jul 15;88(2):756. No abstract available.
- Derived from this study: PubMed 23453583Cortes J, Feldman E, Yee K, Rizzieri D, Advani AS, Charman A, Spruyt R, Toal M, Kantarjian H. Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. Lancet Oncol. 2013 Apr;14(4):354-62. doi: 10.1016/S1470-2045(13)70037-8. Epub 2013 Feb 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge E Cortes, MD principal investigator
M.D. Anderson Cancer Center
Karen Yee, MD principal investigator
Princess Margaret Hospital, Canada
Eric Feldman, MD principal investigator
Weill Cornell Medical College - New York Presbyterian Hospital
21 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tosedostat in people with Acute Myeloid Leukemia and AML, run by Chroma Therapeutics at 21 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Canada, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00780598, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2012.