Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
Ceplene/IL-2 remission maintenance therapy has been shown to significantly prolong Leukemia Free Survival in patients with Acute Myeloid Leukemia (AML) in first complete remission. This is an international, multicenter, open-label study to evaluate the effects of remission maintenance therapy with Ceplene/IL-2 in adult patients with AML in CR1 on specific immune system cells (T and NK cells) and prospectively defined markers of immune response that are known to reflect T and NK cell ability to combat AML.
Acute Myeloid Leukemia
Drug: histamine dihydrochloride and IL-2
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Open-Label, Multicenter, Effects of Remission Maintenance Therapy With Ceplene® , Given in Conjunction With Low-Dose Interleukin-2, on Immune Response and Minimal Residual Disease in Adult Patients With AML in First Complete Remission|
- Minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2 [ Time Frame: Comparison at baseline and various time points up to 2 years ] [ Designated as safety issue: No ]A second primary objective of this study is to evaluate MRD in patients who are receiving remission maintenance therapy with Ceplene/IL-2. MRD will be evaluated using RQ-PCR for molecular detection of genetic markers of AML. Patients' MRD status will be quantified at the time of enrollment (baseline) and within ten days after completion of Cycles 3, 5, 6, 7, 9 and 10 of Ceplene/IL-2 therapy, corresponding to approximately every 3 months during this immunotherapy.
- 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 [ Time Frame: Baseline vs Cycle 1 and 3 ] [ Designated as safety issue: No ]
The quantitative and qualitative pharmacodynamic effects of Ceplene/IL-2 on the immune responses of T and NK cells will be assessed as follows:
- 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.
- Changes in immune response markers (CD3, NKp46 [and other NCRs], CD25, CD69, and IFN-γ) 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
- Duration of LFS [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Duration of LFS: LFS will be defined as the time from achieving CR after successful induction therapy until relapse of AML (defined as 5% or more blast cells in the bone marrow).
|Study Start Date:||July 2009|
|Study Completion Date:||June 2014|
|Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: histamine dihydrochloride and IL-2
histamine and IL-2 subcutaneous injections
Drug: histamine dihydrochloride and IL-2
Ceplene 0.5 mg subcutaneously twice daily and IL-2 1 µg/kg [16,400 IU/kg] body weight twice daily for 10, 21 day cycles
- To assess the quantitative and qualitative pharmacodynamic effects of Ceplene plus low-dose IL-2 (Ceplene/IL-2) by monitoring T and natural killer (NK) cell phenotypes and their functionality after the first and third treatment cycles in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1).
- To evaluate minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2.
To document, in adult AML patients in CR1 treated with Ceplene/IL-2:
- Leukemia-free survival (LFS) after a follow-up period of up to two years.
- The safety of Ceplene/IL-2 therapy.
- The potential relationship of Ceplene/IL-2 effects on T and NK cell phenotypes and their functionality to MRD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01347996
|Sahlgrenska Academy, University of Gothenburg|
|Study Chair:||Robin FOA, MD, PhD||Università degli Studi di Roma "La Sapienza" Dipartimento di Biotecnologie Cellulari ed Ematolgia|
|Principal Investigator:||Mats L Brune, MD, PhD||Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden|