A Study of HDC/IL-2 Treatment in Chronic Myelomonocytic Leukemia (CMML)

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2018
• Main ID: NCT03040401
• Date of registration: 24/01/2017
• Prospective Registration: Yes
• Primary sponsor: Vastra Gotaland Region
• Public title: A Study of HDC/IL-2 Treatment in Chronic Myelomonocytic Leukemia (CMML)
• Scientific title: A Phase I/II, Open-Label, Multicenter Study of the Safety, Efficacy and Immune Response of Histamine Dihydrochloride and Low-dose Interleukin-2 in Chronic Myelomonocytic Leukemia (CMML)
• Date of first enrolment: February 15, 2017
• Target sample size: 15
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03040401
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Sweden

Contacts

• Name: Lars Möllgård, PhD, MD

• Name: Lars Möllgård, PhD, MD
• Affiliation: Sahlgrenska University Hospital, Sweden

Key inclusion & exclusion criteria

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.

- The patient must be informed of the investigational nature of the study and written
informed consent obtained and signed.

- including, but not limited to increasing WBC, transfusion dependence, B-symptoms,
splenomegaly.

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Leukemia, Myelomonocytic, Chronic

Intervention(s)

Drug: Cohort 3, Ceplene® and Proleukin®

Drug: Cohort 1, Ceplene® and Proleukin®

Drug: Cohort 2, Ceplene® and Proleukin®

Primary Outcome(s)

Adverse events as defined by CTCAE v4.03. [Time Frame: 3 weeks after last treatment cycle]

Secondary Outcome(s)

Percentage of circulating CD8+ T cells i peripheral blood [Time Frame: 3 weeks after last treatment cycle]

Proportion of participants with overall survival at 2 years. [Time Frame: 2 years after last treatment cycle]

Number of treated patients that transform to AML [Time Frame: 2 years after last treatment cycle]

Disease progression according to IWG criteria for MDS/MPN [Time Frame: 3 weeks after last treatment cycle]

Percentage of monocytes in peripheral blood [Time Frame: 3 weeks after last treatment cycle]

Percentage of blasts in peripheral blood [Time Frame: 3 weeks after last treatment cycle]

Percentage of circulating CD4+ T cells i peripheral blood [Time Frame: 3 weeks after last treatment cycle]

Percentage of circulating NK cells i peripheral blood [Time Frame: 3 weeks after last treatment cycle]

Secondary ID(s)

NMDSG14A

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Karolinska University Hospital

Nordic MDS Group

Sahlgrenska University Hospital, Sweden