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An Open-Label, Study of Remission Maintenance Therapy With Ceplene® (Histamine), and Low-Dose Interleukin-2, on Immune Response and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission (CR1)

Phase 4
18 Years
Open (Enrolling)
Acute Myeloid Leukemia

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Trial Information

An Open-Label, Study of Remission Maintenance Therapy With Ceplene® (Histamine), and Low-Dose Interleukin-2, on Immune Response and Minimal Residual Disease in Patients With Acute Myeloid Leukemia in First Complete Remission (CR1)

Outcome Measures:


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.


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.

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

- 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

- 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

- 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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2

Outcome Description:

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.

Outcome Time Frame:

Comparison at baseline and various time points up to 2 years

Safety Issue:


Principal Investigator

Robin FOA, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

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


Sweden: Medical Products Agency

Study ID:




Start Date:

July 2009

Completion Date:

June 2015

Related Keywords:

  • Acute Myeloid Leukemia
  • AML
  • Leukemia
  • Acute Myeloid Leukemia
  • Minimal Residual Disease
  • Ceplene
  • Histamine
  • interleukin 2
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Neoplasm, Residual