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

NCT03040401 | Unknown Phase 1

• 1 other identifier: NMDSG14A
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Enrolled subjects will receive histamine dihydrochloride (HDC; Ceplene®) and/or IL-2 (Proleukin®) subcutaneously (s.c.) twice daily (BID) in 3-week periods followed by 3- or 6 week rest periods. All subjects will be assigned to one of three consecutive cohorts, each comprising five patients. Cohort 1 will receive HDC without IL-2 for the first treatment cycle, to enable the assessment of short-term impact of HDC alone on clonal and immunological markers. For all remaining cycles the combination of HDC and IL-2 will be given. Cohort 2 will receive the combination of Ceplene and Proleukin in all cycles. After all patients in cohorts 1 and 2 have completed 4 treatment cycles, immunological and clinical response and toxicity will be evaluated. On the basis of the results for the first 4 cycles of cohorts 1 and 2, a third cohort of 5 patients will be enrolled receiving either the combination of HDC/IL-2 or HDC alone. In case of a beneficial response\* after 4 cycles, treatment may be continued to a total of 10 cycles. Treatment cycles 5-10 will comprise 3 weeks of treatment and 6-week rest periods. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2. The patient or a family member/significant other will be instructed to administer injections of both study drugs to allow safe treatment at home.

Conditions

Leukemia, Myelomonocytic, Chronic

Keywords

CMML; Ceplene; Interleukin-2

Outcome Measures

Primary Outcomes (1)

• Adverse events as defined by CTCAE v4.03.

  3 weeks after last treatment cycle

Secondary Outcomes (8)

• Disease progression according to IWG criteria for MDS/MPN

  3 weeks after last treatment cycle

• Percentage of blasts in peripheral blood

  3 weeks after last treatment cycle

• Percentage of monocytes in peripheral blood

  3 weeks after last treatment cycle

• Number of treated patients that transform to AML

  2 years after last treatment cycle

• Percentage of circulating NK cells i peripheral blood

  3 weeks after last treatment cycle

Study Arms (3)

Cohort 1: Ceplene® and Proleukin®

EXPERIMENTAL

Enrolled subjects will receive histamine dihydrochloride (HDC; Ceplene®) and IL-2 (Proleukin®) subcutaneously (s.c.) twice daily (BID) in 3-week periods followed by 3 week rest periods for a total of 4 treatment cycles. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2 injections. Cohort 1 will receive only Ceplene® during the first treatment cycles and Ceplene® in combination with Proleukin® during treatment cycles 2-4.

Drug: Cohort 1, Ceplene® and Proleukin®

Cohort 2: Ceplene® and Proleukin®

EXPERIMENTAL

Enrolled subjects will receive histamine dihydrochloride (HDC; Ceplene®) and IL-2 (Proleukin®) subcutaneously (s.c.) twice daily (BID) in 3-week periods followed by 3 week rest periods for a total of 4 treatment cycles. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2 injections. Cohort 2 will receive Ceplene® in combination with Proleukin® during all treatment cycles (1-4).

Drug: Cohort 2, Ceplene® and Proleukin®

Cohort 3: Ceplene® and Proleukin®

EXPERIMENTAL

Enrolled subjects will receive histamine dihydrochloride (HDC; Ceplene®) and IL-2 (Proleukin®) subcutaneously (s.c.) twice daily (BID) in 3-week periods followed by 3 week rest periods for a total of 4 treatment cycles. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2 injections. Cohort 3 will receive either only Ceplene® during treatment cycles 1-4 or Ceplene® in combination with Proleukin® during treatment cycles 1-4. Treatment will be decided by the study committee based on the safety profile of treatment administered to cohort 1 and 2.

Drug: Cohort 3, Ceplene® and Proleukin®

Interventions

Cohort 1, Ceplene® and Proleukin® DRUG

Patients in Cohort 1 will be administered only Ceplene® during the first treatment cycles and Ceplene® in combination with Proleukin® during treatment cycles 2-4. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2.

Cohort 1: Ceplene® and Proleukin®

Cohort 2, Ceplene® and Proleukin® DRUG

Patients in Cohort 2 will be administered Ceplene® in combination with Proleukin® during all treatment cycles 1-4. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2.

Cohort 2: Ceplene® and Proleukin®

Cohort 3, Ceplene® and Proleukin® DRUG

Cohort 3 will receive either only Ceplene® during treatment cycles 1-4 or Ceplene® in combination with Proleukin® during treatment cycles 1-4. Treatment will be decided by the study committee based on the safety profile of treatment administered to cohort 1 and 2. IL-2 will be administered s.c., 1 µg/kg (=16400 IU/kg) body weight twice daily (BID) during treatment periods. Ceplene® will be administered s.c. 0.5 mg BID after IL-2.

Cohort 3: Ceplene® and Proleukin®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Sahlgrenska University Hospital: collaborator
• Karolinska University Hospital: collaborator
• Nordic MDS Group: collaborator

Study Sites (2)

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Karolinska University Hospital, Huddinge

Stockholm, Sweden

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Interventions

Histamine; aldesleukin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Lars Möllgård, PhD, MD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lars Möllgård, PhD, MD

CONTACT

+46 (0)31 3427344; lars.mollgard@vgregion.se

Johan Aurelius, PhD

CONTACT

+46 (0)31 7866677; johan.aurelius@gu.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: February 2, 2017
• Study Start: February 15, 2017
• Primary Completion: December 15, 2018
• Study Completion: December 15, 2019
• Last Updated: December 19, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)