A Study of HDC/IL-2 Treatment in Chronic Myelomonocytic Leukemia (CMML)
NCT ID: NCT03040401
Last Updated: 2017-12-19
Study Results
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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UNKNOWN
PHASE1/PHASE2
15 participants
INTERVENTIONAL
2017-02-15
2019-12-15
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Cohort 1: Ceplene® and Proleukin®
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.
Cohort 1, Ceplene® and Proleukin®
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 2: Ceplene® and Proleukin®
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).
Cohort 2, Ceplene® and Proleukin®
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 3: Ceplene® and Proleukin®
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.
Cohort 3, Ceplene® and Proleukin®
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.
Interventions
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Cohort 1, Ceplene® and Proleukin®
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 2, Ceplene® and Proleukin®
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 3, Ceplene® and Proleukin®
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.
Eligibility Criteria
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Inclusion Criteria
* 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
* 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.
18 Years
ALL
No
Sponsors
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Sahlgrenska University Hospital
OTHER
Karolinska University Hospital
OTHER
Nordic MDS Group
NETWORK
Vastra Gotaland Region
OTHER_GOV
Responsible Party
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Principal Investigators
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Lars Möllgård, PhD, MD
Role: PRINCIPAL_INVESTIGATOR
Sahlgrenska University Hospital
Locations
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Sahlgrenska University Hospital
Gothenburg, , Sweden
Karolinska University Hospital, Huddinge
Stockholm, , Sweden
Countries
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Central Contacts
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Facility Contacts
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Lars Möllgård, PhD, MD
Role: primary
Olle Werlenius, PhD, MD
Role: backup
Per Broliden, MD, PhD
Role: primary
Other Identifiers
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NMDSG14A
Identifier Type: -
Identifier Source: org_study_id