A Phase 1/2 interventional study of Ribavirin and Cytarabine arabinoside in Acute Myeloid Leukemia, sponsored by Jewish General Hospital. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-02.
Sponsored by Jewish General Hospital · Phase 1/2, Interventional, and Treatment
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.
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.
STUDY DESIGN AND DURATION
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.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 29 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Jewish General Hospital is the lead sponsor of 95 studies on the registry; 11 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The following patients with acute myeloid leukemia (AML) are eligible:
Exclusion Criteria:
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
Dose level 1 = 1000 mg po BID/ Dose level 2 = 1400 mg po BID/ Dose level 3 = 1800 mg po BID
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
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.
Time frame: 56 days
Overall Response Rate
Overall response rate comprises complete response (\<5% blasts in the bone marrow, and in the peripheral blood Hgb more than or equal to 100 g/L, platelets more than or equal to 100x10-9/L, and neutrophils more than or equal to 1x10-9/L), partial response (5 to 25% blasts in the bone marrow and same peripheral blood parameters) and blast response (a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days).
Time frame: 2-3 years
Complete Response Rate
Defined as \<5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL.
Time frame: 2-3 years
Partial Response
Partial response was defined as 5 to 25% blasts in the bone marrow and Hgb \>100g/L, platelets \>100,000/ul and neutrophils \>1000/ul.
Time frame: 2-3 years
Blast Response
Blast response was defined as a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days.
Time frame: 2-3 years
Patients were enrolled in this dose escalation study according to a 3+3 design. Patients not completing 28 days of therapy were replaced as they were not evaluable for the pharmacokinetic endpoint of steady state level of ribavirin.
| Milestone | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 | Dose Level 6 | Dose Level 7 |
|---|---|---|---|---|---|---|---|
| Started | 4 | 3 | 5 | 6 | 3 | 3 | 5 |
| Completed | 3 | 3 | 3 | 3 | 3 | 3 | 4 |
| Not completed | 1 | 0 | 2 | 3 | 0 | 0 | 1 |
| Withdrew: Death | 1 | 0 | 2 | 3 | 0 | 0 | 1 |
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.
| mg | Ribavirin-Cytarabine |
|---|---|
| Ribavirin po bid for 28 days | 1400 |
| cytarabine arabinoside sc bid for 10 days | 10 |
Overall response rate comprises complete response (\<5% blasts in the bone marrow, and in the peripheral blood Hgb more than or equal to 100 g/L, platelets more than or equal to 100x10-9/L, and neutrophils more than or equal to 1x10-9/L), partial response (5 to 25% blasts in the bone marrow and same peripheral blood parameters) and blast response (a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days).
| Participants | Ribavirin and Cytarabine |
|---|---|
| Overall Response Rate | 5 |
Defined as \<5% blasts in the bone marrow and a hgb 100 g/L, platelets 100,000/uL, neutrophils 1000/uL.
| Participants | Ribavirin and Cytarabine |
|---|---|
| Complete Response Rate | 2 |
Partial response was defined as 5 to 25% blasts in the bone marrow and Hgb \>100g/L, platelets \>100,000/ul and neutrophils \>1000/ul.
| Participants | Ribavirin and Cytarabine |
|---|---|
| Partial Response | 1 |
Blast response was defined as a greater than 50% decrease in bone marrow blast count and 2 log reduction in peripheral blood blast count, sustained for at least 28 days.
| Participants | Ribavirin and Cytarabine |
|---|---|
| Blast Response | 2 |
Collected over 44 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ribavirin-Cytarabine | — | 7/29 (24.1%) | 29/29 (100%) |
| Event | Ribavirin-Cytarabine |
|---|---|
| SyncopeNervous system disorders | 1/29 |
| Exacerbation of bone painMusculoskeletal and connective tissue disorders | 1/29 |
| Cerebrovascular hemorrhageNervous system disorders | 1/29 |
| retinal hemorrhageEye disorders | 1/29 |
| visceral shinglesInfections and infestations | 1/29 |
| Lower gastro-intestinal hemorrhageGastrointestinal disorders | 1/29 |
| SepsisInfections and infestations | 1/29 |
| Event | Ribavirin-Cytarabine |
|---|---|
| anemiaBlood and lymphatic system disorders | 15/29 |
| febrile neutropeniaBlood and lymphatic system disorders | 13/29 |
| mucositisGastrointestinal disorders | 12/29 |
| fatigueGeneral disorders | 12/29 |
| infectionInfections and infestations | 8/29 |
| nauseaGastrointestinal disorders | 7/29 |
| thrombocytopeniaBlood and lymphatic system disorders | 7/29 |
| vomitingGastrointestinal disorders | 6/29 |
| feverGeneral disorders | 6/29 |
| musculoskeletal painMusculoskeletal and connective tissue disorders | 6/29 |
| Age, Continuous(years) | Ribavirin and Cytarabine |
|---|---|
| Median | 65 (22 to 83) |
| Sex: Female, Male(Participants) | Ribavirin and Cytarabine |
|---|---|
| Female | 14 |
| Male | 15 |
| FAB subtype(Participants) | Ribavirin and Cytarabine |
|---|---|
| FAB sutype M4/M5 | 22 |
| Other FAB subtypes | 7 |
This study is completed, as verified in Sep 2023. You cannot join it, but the record below documents what was studied.
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