Hematological DiseasePhase 1CHR-2845-001NCT00820508
Safety and Tolerability of CHR-2845 to Treat Haematological Diseases or Lymphoid Malignancies
A Phase 1 study testing CHR-2845 in people with Hematological Disease and Lymphoid Malignancies, run by Chroma Therapeutics at 4 sites in 3 countries.
Trial summary
The purpose of this study is to determine whether the histone deacetylase inhibitor CHR-2845 is tolerated in patients with haematological diseases and lymphoid malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Disease, Lymphoid Malignancies
- What is being tested?
- CHR-2845
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesin 3 countries
- Study dates
- Dec 2008to Jul 2011
- Phase
- Phase 1
- 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
- Confirmed malignant haematological disease or lymphoid malignancy refractory to standard therapy or for which no standard therapy exists, including acute leukemias, MDS, CML, CLL, CMML, multiple myeloma and Non-Hodgkin's Lymphomas/Hodgkin's disease
- Patients shall have recovered from all acute adverse effects of prior therapies, with the exception of alopecia and grade 1 neuropathy where recovery is not required
- Adequate bone marrow, hepatic and renal function including the following:
- Patients with high blast counts can be included if they can be controlled by the use of hydroxyurea (500 mg -3,000 mg daily).
- Total bilirubin ≤ 1.5 x upper normal limit, excluding cases where elevated bilirubin can be attributed to Gilbert's Syndrome
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- AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit
- Creatinine ≤ 1.5 x upper normal limit
- Age ≥ 18 years
- Performance status (PS) ≤ 2 - Eastern Cooperative Oncology Group (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 start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment.
Who cannot join
- Patients receiving anti-cancer therapy or use of other investigational agents within 21 days prior to trial entry (or a longer period depending on the defined characteristics of the agents used. Bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial. Patients must have recovered from all transient toxicity induced by prior therapy
- Patients with co-existing active infection, graft versus host disease or serious concurrent illness
- Patients who have failed to recover from or after a bone marrow transplantation or haematopoietic stem cell transplantation
- The following diseases are excluded: Burkitt's lymphoma, primary effusion lymphoma, precursor B-cell lymphoblastic lymphoma, symptomatic central nervous system (CNS) lymphoma, CML blast crisis
- Patients with significant cardiovascular disease as defined by:
- history of congestive heart failure requiring therapy
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- history of angina pectoris requiring treatment or myocardial infarction within 6 months prior to trial entry
- presence of severe valvular heart disease
- presence of an atrial or ventricular arrhythmia requiring treatment
- Left Ventricular Ejection Fraction (LVEF) below the normal range at the study centre
- Uncontrolled hypertension
- A history of abnormal QTc intervals or an average QTc interval at screening ≥450 msec
- Any medical or other condition that in the investigator's opinion renders the patient unsuitable for this study due to unacceptable risk
- Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- Gastrointestinal disorders that may interfere with absorption of the study drug
- Patients with known brain tumours or metastases
- More than 6 prior chemotherapy regimens
- Patients requiring growth factor support (erythropoietin, Granulocyte/monocyte Colony Stimulating Factor (GM/CSF), etc)
- Patients requiring palliative radiotherapy within the last 4 weeks prior to study entry
- Uncontrolled hypercalcaemia (CTCAE v3 grade 2 or higher)
- Abnormal plasma potassium or magnesium levels (Common Terminology Criteria for Adverse Events (CTCAE) v3 grade 3 or greater) despite therapy
- Pregnant or breast-feeding women
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Netherlands2 sites
VU University Medical Center
Amsterdam, 1007 MB
Erasmus University Medical Center
Rotterdam, 3015 CE
About this study
Official title: A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-2845, in Patients With Advanced or Treatment Refractory Haematological Diseases or Lymphoid Malignancies
The purpose of this study is to determine whether the histone deacetylase inhibitor CHR-2845 is tolerated in patients with haematological diseases and lymphoid malignancies.
Read the detailed description
CHR-2845 is a novel type of histone deacetylase inhibitor (HDACi) for use in cancer that, in addition to having broad ranging anti-proliferative activity against transformed cells, is designed to have an increased therapeutic window against diseases which involve cells of the monocyte-macrophage lineage. There are several HDACi's in clinical development and one, SAHA (Vorinostat, Zolinza®), has recently been approved for use in the treatment of cutaneous T-cell lymphoma. CHR-2845 is a cell-permeant ester that is metabolised to give an active acid, CHR-2847, which selectively accumulates in monocytes and macrophages. This results in a 20-100 fold increase in anti-proliferative potency of CHR-2845 for monocytic over non-monocytic tumour cells. This selectivity should lead to an increased therapeutic window in haematological malignancies involving cells of the monocyte lineage (AML M4, AML M5 and CMML). In addition, there is increasing evidence that monocytes and macrophages associated with some haematological tumours (tumour-associated macrophages (TAMs)) are involved in supporting the growth and spread of the tumour. This clinical trial will focus on haematological and lymphoid malignancies with the intention of evaluating the safety and tolerability of CHR-2845. Additionally it will compare response in patients where monocytes/macrophages are important disease drivers, with the response in other patients. This will allow an early determination of the potential improvement in therapeutic window afforded by the monocyte/macrophage directed HDACi activity.
- Conditions
- Hematological Disease, Lymphoid Malignancies
- Being tested
- CHR-2845
- Keywords
- Haematological disease, Lymphoid malignancy, Histone deacetylase inhibitor, dose escalation
- Medical subject headings
- Hematologic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CHR-2845Drug
Once daily oral ingestion of capsules (10, 40 or 80mg), dose depending on cohort, treatment cycle of 28 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Oral, once daily administration of CHR-2845 to determine safety and tolerability Receives: Drug: CHR-2845 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD)
Measured: 28 days
Secondary outcomes (1)
To determine pharmacokinetic parameters of CHR-2845 and the active metabolite CHR-2847
Measured: days 1 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2009 (estimated)
- Study startDec 2008
- Primary completionJul 2011
- Study completionJul 2011
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 Hematological DiseaseStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chroma Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bob Löwenberg, M.D, Principal investigator, Erasmus Medical CenterGert Ossenkoppele, M.D, Principal investigator, Amsterdam UMC, location VUmcPierre Zachee, MD, Principal investigator, ZNA StuivenbergNorbert Vey, MD, Principal investigator, Institut Paoli-Calmettes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00820508
- Sponsor's protocol ID
- CHR-2845-001
- Acronym
- CHR-2845-001
- Status last verified
- Nov 2011
- First submitted
- 9 Jan 2009
- Last updated
- 28 Nov 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Ossenkoppele GJ, Lowenberg B, Zachee P, Vey N, Breems D, Van de Loosdrecht AA, Davidson AH, Wells G, Needham L, Bawden L, Toal M, Hooftman L, Debnam PM. A phase I first-in-human study with tefinostat - a monocyte/macrophage targeted histone deacetylase inhibitor - in patients with advanced haematological malignancies. Br J Haematol. 2013 Jul;162(2):191-201. doi: 10.1111/bjh.12359. Epub 2013 May 7.
PubMed 23647373
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Evaluate the Safety and Tolerability of the Histone Deacetylase Inhibitor, CHR-2845, in Patients With Advanced or Treatment Refractory Haematological Diseases or Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT00820508
- Acronym / sponsor ID
- CHR-2845-001 / CHR-2845-001
- Conditions
- Hematological Disease, Lymphoid Malignancies
- Keywords
- Haematological disease, Lymphoid malignancy, Histone deacetylase inhibitor, dose escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Chroma TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 12 Jan 2009 (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 determine whether the histone deacetylase inhibitor CHR-2845 is tolerated in patients with haematological diseases and lymphoid malignancies.
Detailed description
CHR-2845 is a novel type of histone deacetylase inhibitor (HDACi) for use in cancer that, in addition to having broad ranging anti-proliferative activity against transformed cells, is designed to have an increased therapeutic window against diseases which involve cells of the monocyte-macrophage lineage. There are several HDACi's in clinical development and one, SAHA (Vorinostat, Zolinza®), has recently been approved for use in the treatment of cutaneous T-cell lymphoma. CHR-2845 is a cell-permeant ester that is metabolised to give an active acid, CHR-2847, which selectively accumulates in monocytes and macrophages. This results in a 20-100 fold increase in anti-proliferative potency of CHR-2845 for monocytic over non-monocytic tumour cells. This selectivity should lead to an increased therapeutic window in haematological malignancies involving cells of the monocyte lineage (AML M4, AML M5 and CMML). In addition, there is increasing evidence that monocytes and macrophages associated with some haematological tumours (tumour-associated macrophages (TAMs)) are involved in supporting the growth and spread of the tumour. This clinical trial will focus on haematological and lymphoid malignancies with the intention of evaluating the safety and tolerability of CHR-2845. Additionally it will compare response in patients where monocytes/macrophages are important disease drivers, with the response in other patients. This will allow an early determination of the potential improvement in therapeutic window afforded by the monocyte/macrophage directed HDACi activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CHR-2845Oral, once daily administration of CHR-2845 to determine safety and tolerability |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Signed, informed consent
- Confirmed malignant haematological disease or lymphoid malignancy refractory to standard therapy or for which no standard therapy exists, including acute leukemias, MDS, CML, CLL, CMML, multiple myeloma and Non-Hodgkin's Lymphomas/Hodgkin's disease
- Patients shall have recovered from all acute adverse effects of prior therapies, with the exception of alopecia and grade 1 neuropathy where recovery is not required
- Adequate bone marrow, hepatic and renal function including the following:
- Age ≥ 18 years
Key exclusion criteria (22 listed)
- Patients receiving anti-cancer therapy or use of other investigational agents within 21 days prior to trial entry (or a longer period depending on the defined characteristics of the agents used. Bisphosphonates for bone disease and corticosteroids are permitted provided the dose does not change during the trial. Patients must have recovered from all transient toxicity induced by prior therapy
- Patients with co-existing active infection, graft versus host disease or serious concurrent illness
- Patients who have failed to recover from or after a bone marrow transplantation or haematopoietic stem cell transplantation
- The following diseases are excluded: Burkitt's lymphoma, primary effusion lymphoma, precursor B-cell lymphoblastic lymphoma, symptomatic central nervous system (CNS) lymphoma, CML blast crisis
- Patients with significant cardiovascular disease as defined by:
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-2845Once daily oral ingestion of capsules (10, 40 or 80mg), dose depending on cohort, treatment cycle of 28 days | Drug | 1 |
Primary outcome
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD)
Time frame: 28 days
1 secondary outcome
To determine pharmacokinetic parameters of CHR-2845 and the active metabolite CHR-2847
Time frame: days 1 and 28
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 Nov 2011.
- Derived from this study: PubMed 23647373Ossenkoppele GJ, Lowenberg B, Zachee P, Vey N, Breems D, Van de Loosdrecht AA, Davidson AH, Wells G, Needham L, Bawden L, Toal M, Hooftman L, Debnam PM. A phase I first-in-human study with tefinostat - a monocyte/macrophage targeted histone deacetylase inhibitor - in patients with advanced haematological malignancies. Br J Haematol. 2013 Jul;162(2):191-201. doi: 10.1111/bjh.12359. Epub 2013 May 7.
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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.
Bob Löwenberg, M.D principal investigator
Erasmus Medical Center
Gert Ossenkoppele, M.D principal investigator
Amsterdam UMC, location VUmc
Pierre Zachee, MD principal investigator
ZNA Stuivenberg
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CHR-2845 in people with Hematological Disease and Lymphoid Malignancies, run by Chroma Therapeutics at 4 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 12 inclusion and 22 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 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Netherlands, Belgium, France. 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 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.
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?
To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD) (time frame: 28 days). 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 NCT00820508, 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 28 Nov 2011.