Safety and Tolerability of CHR-2845 to Treat Haematological Diseases or Lymphoid Malignancies

NCT00820508 | Completed Phase 1

• 1 other identifier: CHR-2845-001
• Study Type: interventional
• Target: 18
• Locations: 3 countries
• Sites: 4

Brief 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.

Conditions

Hematological Disease; Lymphoid Malignancies

Keywords

Haematological disease; Lymphoid malignancy; Histone deacetylase inhibitor; dose escalation

Outcome Measures

Primary Outcomes (1)

• To determine the safety, tolerability, dose-limiting toxicities (DLT), maximum acceptable dose (MAD) and maximum tolerated dose (MTD)

  28 days

Secondary Outcomes (1)

• To determine pharmacokinetic parameters of CHR-2845 and the active metabolite CHR-2847

  days 1 and 28

Study Arms (1)

1

EXPERIMENTAL

Oral, once daily administration of CHR-2845 to determine safety and tolerability

Drug: CHR-2845

Interventions

CHR-2845 DRUG

Once daily oral ingestion of capsules (10, 40 or 80mg), dose depending on cohort, treatment cycle of 28 days

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Chroma Therapeutics: lead

Study Sites (4)

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Institut Paoli-Calmettes

Marseille, France

Location

VU University Medical Center

Amsterdam, 1007 MB, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 23647373 DERIVED

MeSH Terms

Conditions

Hematologic Diseases

Interventions

CHR 2845

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Study Officials

• Bob Löwenberg, M.D

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Gert Ossenkoppele, M.D

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Pierre Zachee, MD

  ZNA Stuivenberg

  PRINCIPAL INVESTIGATOR

• Norbert Vey, MD

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2009
• First Posted: January 12, 2009
• Study Start: December 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: November 28, 2011

Record last verified: 2011-11

Locations

FR (1); BE (1); NL (2)