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A Phase I/II Study of Ribavirin and Low-dose Cytarabine Arabinoside (Ara-C) in Acute Myeloid Leukemia (AML) M4 and M5 Subtypes, and AML With High eIF4E Expression

Phase 1/Phase 2
18 Years
Open (Enrolling)
Acute Myeloid Leukemia

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Trial Information

A Phase I/II Study of Ribavirin and Low-dose Cytarabine Arabinoside (Ara-C) in Acute Myeloid Leukemia (AML) M4 and M5 Subtypes, and AML With High eIF4E Expression

Primary Objectives

In the Phase I portion of this study, we will determine the maximum tolerated dose and
recommended phase II dose (RP2D) of ribavirin and low-dose ara-C. The primary objective of
the Phase II portion of the study is to determine the overall response rate, including the
complete remission (CR), complete remission with incomplete blood count recovery (CRi),
partial remission (PR) or blast response (BR), to therapy with ribavirin and low dose ara-C
at the RP2D.


This is a multicentre, open-label, single arm Phase I/II study of oral ribavirin and
low-dose ara-C for patients with AML M4/M5 or AML with high expression of eIF4E, who have
relapsed or refractory disease, or who are not suitable candidates for induction
chemotherapy. This study will determine the recommended phase II dose and will evaluate
efficacy. Correlative studies will be included to assess relevant molecular targets.

Inclusion Criteria:

- The following patients with acute myeloid leukemia (AML) are eligible:

- De novo AML M4 or M5 FAB subtype or high eIF4E.

- Secondary AML after a myelodysplastic syndrome (MDS) or a myeloproliferative
disorder (not chronic myelogenous leukemia), if M4 or M5 FAB subtype or high

- Therapy-related AML if M4 or M5 FAB subtype or high eIF4E.

- CML blast crisis if they have failed imatinib and at least one other tyrosine
kinase inhibitor.

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

- 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 expression.

- ECOG performance status 0, 1, 2 or 3.

- Life expectancy > 4 weeks.

- Age is > 18 years.

- Female patients of childbearing potential must have a negative serum (beta-HCG)
pregnancy test within 14 days of starting protocol and must not be breastfeeding. Men
and women of childbearing potential must agree to use an effective means of
contraception throughout the study and for at least 30 days after completion of

- 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.

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

- Accessible for treatment and follow up.

Exclusion Criteria:

- Uncontrolled central nervous system involvement by AML.

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

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

- 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 within 7 days of
starting low dose ara-C and ribavirin.

- Female patients who are pregnant or breastfeeding.

- Concurrent treatment with other anti-cancer therapy.

- Known infection with HIV.

- History of other 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.

- FAB AML M1, 2, 6, 7 will be excluded if they do not have high eIF4E expression. AML
M3 is always excluded.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recommended phase II dose of ribavirin when given in combination with low-dose ara-C

Outcome Time Frame:

6-9 months

Safety Issue:


Principal Investigator

Sarit Assouline, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jewish General Hospital, McGill University


Canada: Health Canada

Study ID:




Start Date:

January 2010

Completion Date:

Related Keywords:

  • Acute Myeloid Leukemia
  • AML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid