Acute Myeloid Leukemia in First Complete Remission (CR1) MedDRA version: 16.1 Level: LLT Classification code 10000887 Term: Acute myeloid leukemia in remission System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Ceplene
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Histamine dihydrochloride
Current Sponsor code: Ceplene
Concentration unit: mg/ml milligram(s)/millilitre
Concentra
Sponsors
MEDA Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • AML patients in CR1 whose AML subtype has been well-characterized using conventional karyotyping and molecular genetic techniques (eg, RQ-PCR) at diagnonsis. Patients may be considered eligible if they have not had this assessment performed at diagnosis provided that stored samples of a diagnostic genetic material (DNA/RNA) from blood and BM are available that can be assayed for the presence of markers such as WT1 and/or AML-specific genetic markers. • Bone marrow examination confirming CR (defined as less than 5% blasts in a normocellular bone marrow). • Eighteen years of age or older. • Patients have received any form of induction and consolidation therapy as per standard practice at the institution, including autologous stem cell transplantation (ASCT). • Within 8 weeks following the date of the last dose of consolidation or conditioning chemotherapy for AML, or following ASCT. • Patients not undergoing consilidation therapy must have been in CR1 for at least one month prior to enrollment. • Platelet count recovered after chemotherapy to =75 x 109/L, and Partial Thromboplastin Time (PTT) within normal limits. • WBC =1.5 x 109/L and LFTs (to include SGPT [ALAT] or SGOT [AST] and bilirubin) should not exceed twice the upper limit of normal. • Serum creatinine less than or equal to 1.5 times the upper normal limit. • Able to function without significant decrease in daily activities (WHO Performance Status 0 - 1 or Karnofsky =70, refer to Appendix 1). • Life expectancy of more than three months and able to undergo routine outpatient evaluations for efficacy, safety, and/or compliance. • Women of childbearing potential must be practicing barrier or oral contraception, for the duration of the treatment, or documented as surgically sterile or one year post-menopausal. • If female, be non-nursing, non-pregnant and have a negative pregnancy test within two weeks of starting study drug. • The patient must be informed of the investigational nature of the study and written informed consent obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: • Patients who have undergone or are planned for allogeneic stem cell transplantation. • Patients with M3 as an AML subtype. • Class III or IV cardiac disease, hypotension or severe hypertension, vasomotor instability, serious or uncontrolled cardiac dysrhythmias (including ventricular arrhythmias) at any time, acute myocardial infarction within the past 12 months, active uncontrolled angina pectoris or symptomatic arteriosclerotic blood vessel disease. • Other active malignancies except in situ carcinoma of the cervix, localized squamous or basal cell carcinoma of the skin. • Serious concurrent or recent non-malignant medical conditions which, in the opinion of the Investigator, makes the patient unsuitable for participation in this study. • History of seizures, central nervous system disorders, stroke within the last 12 months, or psychiatric disability thought to be clinically significant in the opinion of the Investigator and adversely affecting compliance to protocol. • Patients unable to undergo repeat treatments, clinical evaluations and other diagnostic procedures required by the protocol. • Active autoimmune disease (including but not limited to systemic lupus, inflammatory bowel disease, and psoriasis). • Patients with active peptic or esophageal ulcer disease or with past peptic ulcer or esophageal disease with a history or bleeding. • Patients requiring active treatment for hypotension. • Medical, sociologic, or psychological impediment to probable compliance with the protocol. • Patients continuing systemic treatment with clonidine, steroids, and/or H2 receptor blocking agents. • Patients with a history of histamine hypersensitivity, severe allergies to food or contrast media requiring treatment within the last five years. • patients unable to provide written consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of this study are to assess: 1. The quantitative and qualitative pharmacodynamic effects of Ceplene plus low dose IL-2 (Ceplene/IL-2) by monitoring T and NK cell phenotypes and their functionality after the first and third cycles of treatment in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1). 2. Minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2. ;Secondary Objective: The secondary objectives in this study are to document, in AML patients in CR1 treated with Ceplene/IL-2: 1. Leukemia-free survival (LFS) after a follow-up period of up to 2 years. 2. The safety of Ceplene/IL-2 therapy. 4. The potential relationship of Ceplene/IL-2 effects on T and NK cell phenotypes and their functionality to MRD. ;Primary end point(s): Primary Endpoints The quantitative and qualitative pharmacodynamic effects of Ceplene/IL-2 on the immune responses of T and NK cells will be assessed as follows: 1. Changes in T and NK cell phenotypes (CD56, CD3, CD4, CD8) in peripheral blood from Day 1 (baseline) to Day 21 of Cycle 1 and from Day 1 (pre-treatment Cycle 3) to Day 21 of Cycle 3. 2. Changes in immune response markers (CD3, NKp46 [and other NCRs], CD25, CD69, and IFN-?) in peripheral blood from Day 1 (baseline) to Day 21‡ of Cycle 1 and from Day 1 (pre-treatment Cycle 3) to Day 21 of Cycle 3. MRD will be evaluated in patients receiving Ceplene/IL-2 using RQ-PCR techniques. MRD will be determined at enrollment (baseline) and at the end of Cycles 3, 5, 6, 7, 9 and 10, corresponding to approximately every 3 months during Ceplene/IL-2 treatment. At baseline, RQ-PCR will be performed on genetic (DNA/RNA) material extracted from blood and BM samples. All subsequent evaluations of MRD will be performed using genetic material extracted from peripheral blood samples. Patient blood and BM samples are to be sent to a designated center (specified in the Laboratory Manual) that will process these s | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: 1. Duration of LFS: LFS will be defined as the time from CR until relapse of AML (defined as 5% or more blast cells in the bone marrow) or death from any cause (whichever comes first) after a follow-up period of up to 2 years. 2. Ceplene/IL-2 safety: Assessments of clinical symptoms, physical examinations, vital signs, and clinical laboratory tests. 3. Potential relationship of Ceplene/IL-2 effects on T and NK cell phenotypes /functionality to MRD: Analyses of changes in T and NK cell phenotypes/ functionality and levels of MRD from baseline to the end of Cycle 3.;Timepoint(s) of evaluation of this end point: During various timepoints in cycles. | — |
Countries
Belgium, France, Italy, Spain, Sweden, United Kingdom
Contacts
Public ContactDirector Clinical Development
MEDA Pharma GmbH & Co. KG
Outcome results
None listed