Acute Myeloid LeukemiaPhase 1/2NCT00689000
Safety and Anti-Disease Activity of CHR-2797 (Tosedostat) in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM)
A Phase 1/2 study testing CHR-2797 (tosedostat): Aminopeptidase inhibitor in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Chroma Therapeutics at 1 site in United Kingdom.
Trial summary
This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases: Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple Myeloma
- What is being tested?
- CHR-2797 (tosedostat): Aminopeptidase inhibitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2006to Dec 2007
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed, informed consent.
- Patients with AML, MDS (subtype RAEB-1 or RAEB-2), or MM whose disease has relapsed or is refractory to front line and/ or salvage therapy; elderly patients (≥ 60 years) with AML, MDS, MM who are not candidates for chemotherapy and for whom other therapy is inappropriate.
- Patients should have recovered from the acute adverse effects of prior therapies (excluding alopecia and grade II neuropathy).
- AML, MDS and MM are diseases of the haematopoietic system and can cause myelosuppression. Consequently supportive therapy should be given to ensure adequate values, according to local guidelines.
- A bone marrow aspirate/ biopsy performed within four weeks prior to study entry.
- Adequate bone marrow, hepatic and renal function including the following:
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- Patients with high blast counts can be included in the trial, if they can be controlled by the use of hydroxyurea (500-3000 mg daily).
- Total bilirubin ≤ 1.5 x upper normal limit.
- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit.
- Creatinine ≤1.5 x upper normal limit.
- Age ≥ 18 years
- Performance status (PS) ≤ 2 (ECOG scale).
- Estimated life-expectancy greater than 3 months.
- Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of the trial. A woman with reproductive potential is defined as one who is biologically capable of becoming pregnant. Patients who are not surgically sterile or postmenopausal must agree to use a medically acceptable and highly effective method of birth control for the duration of the study and to continue after the end of CHR-2797 treatment for a further 3 months (female patients) or for a further 6 months (for male patients and their partners). A highly effective method of birth control is defined as any method that results in a low failure rate, including implants, injectables, some intra-uterine devices (IUD's), sexual abstinence, and vasectomy/ sterilization. Sexually active males and females using oral contraceptive pills should also use barrier contraception. Although there is no reason to believe that the use of CHR-2797 has an effect on the pharmacokinetics of hormonal contraceptives, this has not yet been proven.
Who cannot join
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry- except for hydroxyurea (maximum daily dose is 3 g).
- Indolent, smouldering myeloma, monoclonal gammopathy with unknown significance.
- Patients who need a daily dose of hydroxyurea greater than 3 g to control leukocytosis.
- Co-existing active infection or serious concurrent illness.
- Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies.
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- Gastrointestinal disorders that may interfere with absorption of the study drug.
- Patients with platelet count(s) < 20,000.
- Patients who have had a blood transfusion (platelet support or packed cells) within 7 days prior to study entry.
- Persistent grade II or greater toxicity from any cause (except haematological toxicities and peripheral neuropathy).
- Patients with grade III-IV peripheral neuropathy.
- Pregnant or breast-feeding women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I-II Study to Evaluate the Safety, Tolerability and Anti-Disease Activity of the Aminopeptidase Inhibitor, CHR-2797, in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia or Multiple Myeloma
This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:
- Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797.
- Phase II: the recommended dose level of CHR-2797, as determined in phase I, will be administered to a further cohort of approximately 40 patients to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study.
Read the detailed description
This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:
Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797. Cohorts of 3-6 patients each will be treated with escalating, once daily, oral doses of CHR-2797 for 84 days (12 weeks), of which the first 28 days constitute the dose finding/ DLT phase. The starting dose will be 60 mg once daily. Doses will be increased in a stepwise fashion by around 40 percent per step until the MTD is reached. The proportion of patients with Multiple Myeloma will be limited to one third: one per cohort of 3 or 2 per cohort of 6. It is anticipated that 24-30 patients will be enrolled in the phase I portion of the trial. A decision will be made with regard to the disease indication to be tested in phase II (either AML/MDS or MM or both), after completion of phase I, or following definition of MTD.
Phase II: the recommended dose as determined in phase I, will be administered for 84 days to a maximum of 40 patients. The primary objective is to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study. A multinomial stopping rule has been included in the design that incorporates objective responses and early progression into a decision to stop or continue this phase I/II trial. An interim assessment will be performed after 15 patients have received the maximum acceptable dose (MAD) dose of CHR-2797 with clearly defined early stopping rules.
There will be a clinical conference at the end of every cohort in the phase I portion of the study, between phase I and II and after the first 15 patients have completed therapy in phase II.
- Being tested
- CHR-2797 (tosedostat): Aminopeptidase inhibitor
- Keywords
- Leukemia, AML, MDS, MM, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, Cancer, Hematological malignancies, Elderly, Refractory, Blood
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Multiple Myeloma, Leukemia, Neoplasms, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHR-2797 (tosedostat): Aminopeptidase inhibitorDrug
Also called tosedostat, CHR-2797, aminopeptidase inhibitor
Phase I: Once daily, oral ingestion of CHR-2797 capsules (60mg, 90mg, 130mg or 180mg) depending on cohort
Phase II: Once daily, oral ingestion of 130mg CHR-2797 (recommended dose from Phase I) until progressive disease or withdrawal from the study
| Study group | Role | What they receive |
|---|---|---|
| CHR-2797 (tosedostat) | Experimental | oral, once daily administration of CHR-2797 to determine safety \& anti-disease activity. Receives: Drug: CHR-2797 (tosedostat): Aminopeptidase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily.
Measured: first 28 days of treatment
Phase II: To evaluate the anti-leukaemia/myeloma effect of the recommended dose of single agent CHR-2797.
Measured: End of study
Secondary outcomes (2)
Phase I and II: To determine trough levels of CHR-2797 when administered orally, once daily, at different dose levels.
Measured: End of study
Phase II: To evaluate the safety and tolerability of the recommended dose of CHR-2797 when administered orally, once daily.
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2008 (estimated)
- Study startMay 2006
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chroma Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Gareth Morgan, MD, Principal investigator, Royal Marsden Hospital, UKGert Ossenkoppele, MD, Principal investigator, Vrije Universiteit MC, AmsterdamPierre Zachée, MD, Principal investigator, ZNA Antwerpen, BelgiumAlan Burnett, MD, Principal investigator, University Hospital, Cardiff, United KingdomMichel Delforge, MD, Principal investigator, UZ Gasthuisberg, Leuven, BelgiumBob Lowenberg, MD, Principal investigator, Erasmus MC, RotterdamUlrich Dührsen, MD, Principal investigator, Universitätsklinikum, Essen, GermanyCarsten Müller-Tidow, MD, Principal investigator, Universitätsklinikum, Münster, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00689000
- Sponsor's protocol ID
- CHR-2797-002
- Status last verified
- Oct 2010
- First submitted
- 29 May 2008
- Last updated
- 22 Oct 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lowenberg B, Morgan G, Ossenkoppele GJ, Burnett AK, Zachee P, Duhrsen U, Dierickx D, Muller-Tidow C, Sonneveld P, Krug U, Bone E, Flores N, Richardson AF, Hooftman L, Jenkins C, Zweegman S, Davies F. Phase I/II clinical study of Tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia. J Clin Oncol. 2010 Oct 1;28(28):4333-8. doi: 10.1200/JCO.2009.27.6295. Epub 2010 Aug 23.
PubMed 20733120
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study to Evaluate the Safety, Tolerability and Anti-Disease Activity of the Aminopeptidase Inhibitor, CHR-2797, in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia or Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00689000
- Acronym / sponsor ID
- CHR-2797-002
- Keywords
- Leukemia, AML, MDS, MM, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Chroma TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 3 Jun 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.
This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:
- Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797.
- Phase II: the recommended dose level of CHR-2797, as determined in phase I, will be administered to a further cohort of approximately 40 patients to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study.
Detailed description
This is an open-label, non-randomised, multi-centre phase I-II study of CHR-2797 administered orally once a day. The study involves two distinct phases:
Phase I: an open-label, dose-escalating phase of the study to explore the safety, tolerability, and pharmacokinetics (PK) of CHR-2797. Cohorts of 3-6 patients each will be treated with escalating, once daily, oral doses of CHR-2797 for 84 days (12 weeks), of which the first 28 days constitute the dose finding/ DLT phase. The starting dose will be 60 mg once daily. Doses will be increased in a stepwise fashion by around 40 percent per step until the MTD is reached. The proportion of patients with Multiple Myeloma will be limited to one third: one per cohort of 3 or 2 per cohort of 6. It is anticipated that 24-30 patients will be enrolled in the phase I portion of the trial. A decision will be made with regard to the disease indication to be tested in phase II (either AML/MDS or MM or both), after completion of phase I, or following definition of MTD.
Phase II: the recommended dose as determined in phase I, will be administered for 84 days to a maximum of 40 patients. The primary objective is to determine whether CHR-2797 has sufficient biological activity against the disease(s) under study. A multinomial stopping rule has been included in the design that incorporates objective responses and early progression into a decision to stop or continue this phase I/II trial. An interim assessment will be performed after 15 patients have received the maximum acceptable dose (MAD) dose of CHR-2797 with clearly defined early stopping rules.
There will be a clinical conference at the end of every cohort in the phase I portion of the study, between phase I and II and after the first 15 patients have completed therapy in phase II.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CHR-2797 (tosedostat) | Experimental | Drug: CHR-2797 (tosedostat): Aminopeptidase inhibitororal, once daily administration of CHR-2797 to determine safety \& anti-disease activity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed, informed consent.
- Patients with AML, MDS (subtype RAEB-1 or RAEB-2), or MM whose disease has relapsed or is refractory to front line and/ or salvage therapy; elderly patients (≥ 60 years) with AML, MDS, MM who are not candidates for chemotherapy and for whom other therapy is inappropriate.
- Patients should have recovered from the acute adverse effects of prior therapies (excluding alopecia and grade II neuropathy).
- AML, MDS and MM are diseases of the haematopoietic system and can cause myelosuppression. Consequently supportive therapy should be given to ensure adequate values, according to local guidelines.
- A bone marrow aspirate/ biopsy performed within four weeks prior to study entry.
Key exclusion criteria (12 listed)
- Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 4 weeks prior to trial entry- except for hydroxyurea (maximum daily dose is 3 g).
- Indolent, smouldering myeloma, monoclonal gammopathy with unknown significance.
- Patients who need a daily dose of hydroxyurea greater than 3 g to control leukocytosis.
- Co-existing active infection or serious concurrent illness.
- Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study
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 |
|---|---|---|
| CHR-2797 (tosedostat): Aminopeptidase inhibitorAlso: tosedostat, CHR-2797, aminopeptidase inhibitorPhase I: Once daily, oral ingestion of CHR-2797 capsules (60mg, 90mg, 130mg or 180mg) depending on cohort Phase II: Once daily, oral ingestion of 130mg CHR-2797 (recommended dose from Phase I) until progressive disease or withdrawal from the study | Drug | CHR-2797 (tosedostat) |
Primary outcome
Phase I: To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily.
Time frame: first 28 days of treatment
Phase II: To evaluate the anti-leukaemia/myeloma effect of the recommended dose of single agent CHR-2797.
Time frame: End of study
2 secondary outcomes
Phase I and II: To determine trough levels of CHR-2797 when administered orally, once daily, at different dose levels.
Time frame: End of study
Phase II: To evaluate the safety and tolerability of the recommended dose of CHR-2797 when administered orally, once daily.
Time frame: End of study
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 22 Oct 2010.
- Results publication: PubMed 20733120Lowenberg B, Morgan G, Ossenkoppele GJ, Burnett AK, Zachee P, Duhrsen U, Dierickx D, Muller-Tidow C, Sonneveld P, Krug U, Bone E, Flores N, Richardson AF, Hooftman L, Jenkins C, Zweegman S, Davies F. Phase I/II clinical study of Tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia. J Clin Oncol. 2010 Oct 1;28(28):4333-8. doi: 10.1200/JCO.2009.27.6295. Epub 2010 Aug 23.
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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.
Gareth Morgan, MD principal investigator
Royal Marsden Hospital, UK
Gert Ossenkoppele, MD principal investigator
Vrije Universiteit MC, Amsterdam
Pierre Zachée, MD principal investigator
ZNA Antwerpen, Belgium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CHR-2797 (tosedostat): Aminopeptidase inhibitor in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Chroma Therapeutics at 1 site in United Kingdom.
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 14 inclusion and 12 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 22 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Phase I: To determine the safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of CHR-2797 when administered orally, once daily. (time frame: first 28 days of treatment). The study lists 2 primary outcomes in all. 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 NCT00689000, which also lists 1 linked publication.
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 22 Oct 2010.