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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

Phase 1/Phase 2
18 Years
Not Enrolling
Acute Myeloid Leukemia, Myelodysplastic Syndrome, Multiple Myeloma

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Trial Information

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. 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.

Inclusion Criteria:

- 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:

1. 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).

2. Total bilirubin ≤ 1.5 x upper normal limit.

3. AST (SGOT), ALT (SGPT) ≤ 2.5 x upper normal limit.

4. 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.

Exclusion Criteria:

- 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

- 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

- 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 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Time Frame:

first 28 days of treatment

Safety Issue:


Principal Investigator

Gareth Morgan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Royal Marsden Hospital, UK


Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment

Study ID:




Start Date:

May 2006

Completion Date:

December 2007

Related Keywords:

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • Multiple Myeloma
  • Leukemia
  • AML
  • MDS
  • MM
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndrome
  • Multiple Myeloma
  • Cancer
  • Hematological malignancies
  • Elderly
  • Refractory
  • Blood
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia