Use of Ribavirin and Low Dose Ara-C to Treat Acute Myeloid Leukemia

NCT01056523 | Completed Phase 1 Results

• 1 other identifier: Ribavirin-002
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the maximum tolerated dose of ribavirin, when given in combination with low-dose ara-C and to determine if it is safe and well-tolerated in patients with acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II Dose (RP2D) of Ribavirin When Given in Combination With Low-dose Ara-C

  This 3+3 designed aimed to determine recommended phase II dose (RP2D) based on pharmacokinetics (PK) and maximum tolerated dose (MTD). For the dose to be selected, a target steady state level of ribavirin 20 uM was needed for all patients and no more than 1 of 6 patients could have had dose limiting toxicity at that dose.

  56 days

Secondary Outcomes (4)

• Overall Response Rate

  2-3 years

• Complete Response Rate

  2-3 years

• Partial Response

  2-3 years

• Blast Response

  2-3 years

Study Arms (1)

Ribavirin-Cytarabine arabinoside

EXPERIMENTAL

Ribavirin will be given orally bid according to a dose escalation scheme daily for 28 days of a 28 day cycle Cytarabine arabinoside will be given 20 mg sc bid days 1 to 10 of a 28 day cycle

Drug: Ribavirin; Drug: Cytarabine arabinoside

Interventions

Ribavirin DRUG

Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BID

Ribavirin-Cytarabine arabinoside

Cytarabine arabinoside DRUG

Previous cohorts at 20 mg bid days 1 to 10 of every 28 day cycle. Dosage modified to 10 mg bid days 1 to 10 of every 28 day cycle for more recent cohorts.

Also known as: Ara-C

Ribavirin-Cytarabine arabinoside

Eligibility Criteria

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

You may qualify if:

• 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 eIF4E.
• 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 protocol.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jewish General Hospital: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (1)

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (2)

• Assouline S, Culjkovic B, Cocolakis E, Rousseau C, Beslu N, Amri A, Caplan S, Leber B, Roy DC, Miller WH Jr, Borden KL. Molecular targeting of the oncogene eIF4E in acute myeloid leukemia (AML): a proof-of-principle clinical trial with ribavirin. Blood. 2009 Jul 9;114(2):257-60. doi: 10.1182/blood-2009-02-205153. Epub 2009 May 11.

  PMID: 19433856 BACKGROUND

• Assouline S, Culjkovic-Kraljacic B, Bergeron J, Caplan S, Cocolakis E, Lambert C, Lau CJ, Zahreddine HA, Miller WH Jr, Borden KL. A phase I trial of ribavirin and low-dose cytarabine for the treatment of relapsed and refractory acute myeloid leukemia with elevated eIF4E. Haematologica. 2015 Jan;100(1):e7-9. doi: 10.3324/haematol.2014.111245. Epub 2014 Nov 25. No abstract available.

  PMID: 25425688 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Ribavirin; Arabinofuranosylcytosine Triphosphate; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleotides; Nucleotides; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides

Limitations and Caveats

There were no limitations or caveats

Results Point of Contact

• Title: Dr. Assouline
• Organization: Jewish General Hospital

sarit.assouline@mcgill.ca

514-340-8222

Study Officials

• Sarit Assouline, MD

  Jewish General Hospital, McGill University

  PRINCIPAL INVESTIGATOR

• Katherine Borden, PhD

  Université de Montréal

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2010
• First Posted: January 26, 2010
• Study Start: January 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 2, 2023
• Results First Posted: January 30, 2017

Record last verified: 2023-09

Locations

CA (1)