Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia

NCT ID: NCT01347996

Last Updated: 2017-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-31

Study Completion Date

2014-06-30

Brief Summary

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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.

Detailed Description

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Outcome Measures:

Primary:

1. 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).
2. To evaluate minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2.

Secondary:

To document, in adult AML patients in CR1 treated with Ceplene/IL-2:

1. Leukemia-free survival (LFS) after a follow-up period of up to two years.
2. The safety of Ceplene/IL-2 therapy.
3. The potential relationship of Ceplene/IL-2 effects on T and NK cell phenotypes and their functionality to MRD.

Conditions

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Acute Myeloid Leukemia

Keywords

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AML Leukemia Acute Myeloid Leukemia Minimal Residual Disease Ceplene Histamine interleukin 2

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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histamine dihydrochloride and IL-2

histamine and IL-2 subcutaneous injections

Group Type EXPERIMENTAL

histamine dihydrochloride and IL-2

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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Ceplene Proleukin IL-2 interleukin-2 histamine

Eligibility Criteria

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Inclusion Criteria

* AML patients in CR1 whose AML subtype has been well-characterized using conventional karyotyping and molecular genetic techniques (eg, RQ-PCR) at diagnosis. Patients may be considered eligible if they have not had this assessment performed at diagnosis provided that stored samples of 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 consolidation 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).
* 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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EpiCept Corporation

INDUSTRY

Sponsor Role collaborator

Cytovia, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robin FOA, MD, PhD

Role: STUDY_CHAIR

Università degli Studi di Roma "La Sapienza" Dipartimento di Biotecnologie Cellulari ed Ematolgia

Mats L Brune, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska Academy University of Gothenburg, Gothenburg, Sweden

Locations

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Sahlgrenska Academy, University of Gothenburg

Gothenburg, , Sweden

Site Status

Countries

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Sweden

References

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Hussein BA, Hallner A, Wennstrom L, Brune M, Martner A, Hellstrand K, Bernson E, Thoren FB. Impact of NK Cell Activating Receptor Gene Variants on Receptor Expression and Outcome of Immunotherapy in Acute Myeloid Leukemia. Front Immunol. 2021 Dec 9;12:796072. doi: 10.3389/fimmu.2021.796072. eCollection 2021.

Reference Type DERIVED
PMID: 34956230 (View on PubMed)

Grauers Wiktorin H, Aydin E, Christenson K, Issdisai N, Thoren FB, Hellstrand K, Martner A. Impact of IL-1beta and the IL-1R antagonist on relapse risk and survival in AML patients undergoing immunotherapy for remission maintenance. Oncoimmunology. 2021 Jul 25;10(1):1944538. doi: 10.1080/2162402X.2021.1944538. eCollection 2021.

Reference Type DERIVED
PMID: 34367728 (View on PubMed)

Grauers Wiktorin H, Nilsson MS, Kiffin R, Sander FE, Lenox B, Rydstrom A, Hellstrand K, Martner A. Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade. Cancer Immunol Immunother. 2019 Feb;68(2):163-174. doi: 10.1007/s00262-018-2253-6. Epub 2018 Oct 12.

Reference Type DERIVED
PMID: 30315349 (View on PubMed)

Sander FE, Nilsson M, Rydstrom A, Aurelius J, Riise RE, Movitz C, Bernson E, Kiffin R, Stahlberg A, Brune M, Foa R, Hellstrand K, Thoren FB, Martner A. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy. Cancer Immunol Immunother. 2017 Nov;66(11):1473-1484. doi: 10.1007/s00262-017-2040-9. Epub 2017 Jul 18.

Reference Type DERIVED
PMID: 28721449 (View on PubMed)

Bernson E, Hallner A, Sander FE, Wilsson O, Werlenius O, Rydstrom A, Kiffin R, Brune M, Foa R, Aurelius J, Martner A, Hellstrand K, Thoren FB. Impact of killer-immunoglobulin-like receptor and human leukocyte antigen genotypes on the efficacy of immunotherapy in acute myeloid leukemia. Leukemia. 2017 Dec;31(12):2552-2559. doi: 10.1038/leu.2017.151. Epub 2017 May 22.

Reference Type DERIVED
PMID: 28529313 (View on PubMed)

Rydstrom A, Hallner A, Aurelius J, Sander FE, Bernson E, Kiffin R, Thoren FB, Hellstrand K, Martner A. Dynamics of myeloid cell populations during relapse-preventive immunotherapy in acute myeloid leukemia. J Leukoc Biol. 2017 Aug;102(2):467-474. doi: 10.1189/jlb.5VMA1116-455R. Epub 2017 Feb 24.

Reference Type DERIVED
PMID: 28235771 (View on PubMed)

Sander FE, Rydstrom A, Bernson E, Kiffin R, Riise R, Aurelius J, Anderson H, Brune M, Foa R, Hellstrand K, Thoren FB, Martner A. Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia. Oncotarget. 2016 Feb 16;7(7):7586-96. doi: 10.18632/oncotarget.7210.

Reference Type DERIVED
PMID: 26863635 (View on PubMed)

Other Identifiers

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EPC2008-02

Identifier Type: -

Identifier Source: org_study_id