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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official 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)

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.


Detailed Summary:
Sponsor: Vastra Gotaland Region

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Disease progression according to IWG criteria for MDS/MPN [ Time Frame: 3 weeks after last treatment cycle ]
  • Percentage of blasts in peripheral blood [ Time Frame: 3 weeks after last treatment cycle ]
    Percentage of blasts (CD34+ cells and promonocytes) will be assessed by flow cytometry. End-of-treatment percentage will be compared to values pre-study.
  • Percentage of monocytes in peripheral blood [ Time Frame: 3 weeks after last treatment cycle ]
    Percentage of CD14+ monocytes will be assessed by flow cytometry. End-of-treatment percentage will be compared to values pre-study.
  • Number of treated patients that transform to AML [ Time Frame: 2 years after last treatment cycle ]
  • Percentage of circulating NK cells i peripheral blood [ Time Frame: 3 weeks after last treatment cycle ]
    Percentage of NK cells in peripheral blood will be assessed by flow cytometry. End-of-treatment percentage will be compared to values pre-study.
  • Percentage of circulating CD4+ T cells i peripheral blood [ Time Frame: 3 weeks after last treatment cycle ]
    Percentage of CD4+ T cells in peripheral blood will be assessed by flow cytometry. End-of-treatment percentage will be compared to values pre-study.
  • Percentage of circulating CD8+ T cells i peripheral blood [ Time Frame: 3 weeks after last treatment cycle ]
    Percentage of CD8+ T cells in peripheral blood will be assessed by flow cytometry. End-of-treatment percentage will be compared to values pre-study.
  • Proportion of participants with overall survival at 2 years. [ Time Frame: 2 years after last treatment cycle ]


Original Secondary Outcome: Same as current

Information By: Vastra Gotaland Region

Dates:
Date Received: January 24, 2017
Date Started: February 15, 2017
Date Completion: December 15, 2019
Last Updated: April 28, 2017
Last Verified: January 2017