Clinical Trials /

Ribavirin and Hedgehog Inhibitor With or Without Decitabine in AML

NCT02073838

Description:

This is a research study of ribavirin which will be given in combination with vismodegib and/or decitabine. The purpose of this study is to see if patients respond to treatment when ribavirin is given with vismodegib alone or in combination with decitabine.

Related Conditions:
  • Acute Monocytic Leukemia
  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia Not Otherwise Specified
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ribavirin and Hedgehog Inhibitor With or Without Decitabine in AML
  • Official Title: A Phase II, Multi-center, Open Label, Randomized Study of Ribavirin and Hedgehog Inhibitor With or Without Decitabine in Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: Ribavirin=005
  • NCT ID: NCT02073838

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
RibavirinRibavirin, vismodegib, decitabine
VismodegibRibavirin, vismodegib, decitabine
DecitabineRibavirin, vismodegib, decitabine

Purpose

This is a research study of ribavirin which will be given in combination with vismodegib and/or decitabine. The purpose of this study is to see if patients respond to treatment when ribavirin is given with vismodegib alone or in combination with decitabine.

Trial Arms

NameTypeDescriptionInterventions
Ribavirin, vismodegib, decitabineExperimentalDecitabine 20mg/m2 IV QD days -7 to -3 for cycle 1. Ribavirin 1400mg BID and vismodegib 150mg QD starting on day 1. On subsequent cycles, decitabine will be administered on days 1 to 5.
  • Ribavirin
  • Vismodegib
  • Decitabine
Ribavirin, vismodegibExperimentalRibavirin 1400mg BID, vismodegib 150mg QD
  • Ribavirin
  • Decitabine

Eligibility Criteria

        INCLUSION CRITERIA

          1. Patients with AML M4 or M5 FAB subtype or high eIF4E are eligible.

          2. All patients must have failed primary therapy (defined as two induction
             chemotherapies), must have relapsed, or must not be suitable candidates for intensive
             induction chemotherapy.

          3. Patients who have a dry aspirate or extramedullary disease only are eligible for this
             study if they have a pre-treatment marrow or tissue biopsy demonstrating AML M4 or M5
             subtype or high eIF4E.

          4. ECOG performance status 0, 1, 2.

          5. Life expectancy>4 weeks.

          6. Age is > 18 years.

          7. Female patients of childbearing potential (FCBP) is defined as a sexually mature woman
             who: 1) has not undergone a hysterectomy or bilateral oophorectomy, or 2) has not been
             naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
             any time in the preceding 24 consecutive months). In addition, women under the age of
             55 years must have a serum follicle stimulating hormone (FSH) level > 40IU/L to
             confirm menopause.

             FCBP must have a negative serum (beta-HCG) pregnancy test (minimum sensitivity 25 IU/L
             of equivalent units of HCG) within 7 days of starting treatment and must not be
             breastfeeding. Men and females of childbearing potential must agree to use two
             effective means of contraception, with one method being highly effective and the other
             method being either highly effective or less effective as listed below throughout the
             study and for at least 24 months after completion of protocol.

             An effective means of contraception includes the following:

             i. Male condoms with spermicide ii. Hormonal methods of contraception including
             combined oral contraception pills, vaginal ring, injectables, implants, and
             intrauterine devices (IUDs).

             iii. Nonhormonal IUDs iv. Tubal ligation v. Vasectomy vi. Complete Abstinence

             A less effective means of contraception includes the following:

             i. Diaphragm with spermicide ii. Vaginal sponge iii. Male condom without spermicide
             iv. Progestin only pills by females of childbearing potential or male subject's FCBP
             partners v. Female condom (a male and female condom must not be used together)

             Male subjects must not donate semen while on study and during 24 months after
             treatment discontinuation.

          8. Adequate renal and hepatic function: serum creatinine < 1.5 x ULN; AST or ALT < 2.5 x
             ULN (or < 5 x ULN if liver involvement with leukemia); serum bilirubin < 1.5 x ULN

          9. Provide written consent after the investigational nature, study design, risks and
             benefits of the study have been explained.

         10. Accessible for treatment and follow up.

        EXCLUSION CRITERIA

          1. Patients with impaired ribavirin uptake. As tested in the central laboratory.

          2. Uncontrolled central nervous system involvement by AML.

          3. Active cardiovascular disease as defined by New York Heart Association (NYHA) class
             III-IV categorization.

          4. Patients with hemoglobinopathies which may affect their ability to tolerate ribavirin.

          5. Intercurrent illness or medical condition precluding safe administration of the
             planned protocol treatment or required follow-up.

          6. Received any previous therapy for AML within 28 days prior to the study entry. Hydrea
             is permitted for the treatment of leukocytosis but must be stopped prior to starting
             study drugs.

          7. Female patients who are pregnant or breastfeeding.

          8. Concurrent treatment with other anti-cancer therapy except adjuvant antihormonal
             agents for breast cancer or for limited stage prostate cancer.

          9. Known infection with HIV.

         10. History of other active malignancy. Subjects who have been disease-free for 2 year or
             subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma are eligible.

         11. FAB AML M1, 2, 6, 7 will be excluded if they do not have high eIF4E expression. AML M3
             is always excluded.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Efficacy will be measured by overall response rate (ORR).
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to response
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:One year survival
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Measured up to 3 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:Hematologic improvement defined by the number of individual, positively affected cell lines (erythroid, neutrophil and platelet cells) per patient.
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:Number of participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:
Measure:Changes in eIF4E expression, localization, and signalling pathways (measured by immuno-histochemical analysis, PCR or western blot) and correlating with each patient's overall response.
Time Frame:Measured up to 2 years after the last subject has enrolled in the study.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarit Assouline

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