A study to evaluate safety and efficiency of treatment with histamine and interleukin-2 in chronic myelomonocytic leukemia (CMML)

Phase 1

• Conditions: Chronic myelomonocytic leukemia; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004874-41-SE
• Lead Sponsor: ordic MDS study group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-02
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

• =18 years of age at the time of signing the informed consent form.
• CMML-1 with indication for treatment according to NMDSG
guidelines*.
• Life expectancy of more than three months and ability to undergo
routine outpatient evaluations for efficacy, safety, and compliance.
• Informed consent obtained and signed.
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 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

• Acute myeloid leukemia.
• CMML-2 according to WHO criteria.
• Systemic mastocytosis.
• Previous or intended allogeneic stem cell transplantation.
• Concomitant or intended cytostatic or cytoreductive therapy other
than hydroxyurea (HU) *.
• ECOG performance status =3.
• Platelet count (TPK) <30x109/L
• NYHA 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, 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.
• Serum creatinine > 1.5 times the upper normal limit.
• Serum aminotransferase (AST), alanine transaminase (ALT) and
bilirubin >2.0 times the upper normal limit
• 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.
• 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.
• Pregnancy. Women of childbearing potential (WCBP) and males
having intercourse with WCBP must agree to comply with using an
effective contraceptive method for the duration of the treatment (WCBP
is a sexually mature woman who is not surgically sterile or has not been
naturally postmenopausal for at least 12 consecutive months).
• Nursing
* Note that treatment with HU is allowed if treatment has been ongoing
for at least 3 months prior to enrollment. The use of HU is also allowed
to control myeloproliferation after starting study treatment, preferably
during resting periods Please refer to section 9.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Main Objective: To evaluate the safety and feasibility of treatment with HDC/IL-2 in<br> CMML<br> ;<br> Secondary Objective: To evaluate the clinical efficacy of HDC/IL-2 treatment in CMML.<br> To investigate the immunological effects of HDC/IL-2 in CMML<br> ;Primary end point(s): • Adverse events as defined by CTCAE v4.03.;<br> Timepoint(s) of evaluation of this end point: Continuously from starting treatment until 30 days after end of<br> treatment<br>

Secondary Outcome Measures

Name	Time	Method
<br> Timepoint(s) of evaluation of this end point: Safety endpoints will be assessed continuously from starting treatment<br> until 30 days after end of treatment. Efficacy and immunological<br> endpoints will be evaluated after 4 and 10 treatment cycles.<br> ;<br> Secondary end point(s): • Clinical response and hematological improvement, and durations<br> thereof, according to IWG criteria for MDS/MPN<br> • Changes in size, genotype and phenotype of the malignant<br> populations.<br> • Correlation between genetic aberrations and clinical response.<br> • The quantitative and qualitative effects of HDC/IL-2 on immune cell<br> phenotypes and function.<br> • Disease progression according to IWG criteria for MDS/MPN(1).<br> • Transformation to AML.<br> • Allo-SCT.<br> • Survival.<br>