Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction for Acute Myelid Leukemia (V-FIRST)
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| ClinicalTrials.gov Identifier: NCT03455504 |
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Recruitment Status :
Active, not recruiting
First Posted : March 6, 2018
Last Update Posted : January 10, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia | Drug: Venetoclax | Phase 2 |
Intensive treatment of Acute Leukemia, multidrug based chemotherapy induction, achieves complete remission (CR) rates ranging from 50% to 80%. Nonetheless, the majority (60- 70%) of responding patients will eventually relapse.
Patients with non-low risk leukemia according most diffuse risk scores have a poor prognosis and a short survival. For these patient traditional chemotherapy seems to be ineffective, even with BMT consolidation, probably due to activation of survival pathways in Leukemia cells, so that novel therapeutic interventions should be attempted.
This study will test the effectiveness and safety of Venetoclax, a selective BCL2 inhibitor, in combination with standard induction regimen.
Inhibiting anti-apoptotic pathway of BCL2, the investigators expect to improve success rate of standard chemotherapies.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 124 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Study run-in and phase II |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Study Investigating Safety, Tolerability and Effectiveness of Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction of New Onset Non-M3 Acute Myelid Leukemia |
| Actual Study Start Date : | October 26, 2018 |
| Estimated Primary Completion Date : | January 2025 |
| Estimated Study Completion Date : | January 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1
FLAI + V400 mg
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Drug: Venetoclax
Venetoclax add in combination with fludarabine, cyratabine and idarubicine |
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Experimental: Cohort 2
FLAI + V600 mg
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Drug: Venetoclax
Venetoclax add in combination with fludarabine, cyratabine and idarubicine |
- Number of patients achieving complete response (CR) after course 1 or course 2 if course 2 is administered (CR + CRi + CRp) [ Time Frame: At 24 months from study entry ]Efficacy in new onset, non ELN Low risk AML (safety run-in, part1, and part2). Effectiveness of Venetoclax added in combination with chemotherapy in obtaining Complete remission in new onset, non ELN Low risk AML (safety run-in, part1, and part2).
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with documented/confirmed new onset non-m3 acute myeloid leukemia, according to WHO 2017 will be eligible for this study.
- Hematological illness has to be graded intermediate or high risk according ELN criteria
- Patients ≥ 18 years old and ≤ 65 years old
- ECOG performance status ≤ 2.
- Patients with a life expectancy >12 weeks
- Patients may have AML which has arisen from prior therapies or other antecedent disorder
- Adequate hepatic function
- Adequate pancreatic function
- Adequate renal function assessed by: Serum creatinine within reference laboratory ranges or creatinine clearance (by Cockcroft Gault formula, see Appendix 2) ≥ 50 mL/min for patients in whom, in the Investigator's judgment, serum creatinine level may not adequately reflect renal function.
- All non-hematological adverse events must have resolved to NCI-CTCAE Grade ≤ 2 prior to starting therapy.
- Patients must be considered by Investigator suitable to receive combination chemotherapy.
- Combination chemotherapy has not to be considered toxic without expectation of any benefit for the patient
- For females of childbearing potential, a negative pregnancy test must be documented within 72 hours prior to the first study drug administration.
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All patients must be willing to use effective methods of contraception, during the treatment period and for 100 days after the last dose of Venetoclax. Female patients must be postmenopausal (≥ 1 year of amenorrhea), surgically sterile, or they must agree to use 2 adequate methods of contraception with at least one method with a failure rate of
≤ 1% per year (e.g., hormonal implants, combined oral contraceptives, vasectomized partner) and the second preferably a physical barrier method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Male patients must be surgically sterile or agree to use an acceptable method of contraception.
- Patient must be willing to submit the blood sampling and bone marrow sampling for the PK and PD analyses and exploratory biomarkers.
- Ability to understand and willingness to sign an informed consent form.
- Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
Exclusion Criteria:
- Patients with low risk AML according ELN criteria
- Patients with current clinical evidence of CNS leukemia.
- Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of Hydroxyurea (HU) or 6-Mercaptopurine (6MP) in patients who need to continue this agent to maintain WBC count ≤10,000/mm3. HU and 6MP must be discontinued at the time of initiation of study medications.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study including but not limited at:
- unstable angina
- Patients who are on anti-microbial agents with therapeutic intent
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03455504
Show 22 study locations
| Study Chair: | Giovanni Martinelli | Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) Meldola | |
| Study Director: | Fabio Ciceri | Istituto S. Raffaele, Milan |
| Responsible Party: | Gruppo Italiano Malattie EMatologiche dell'Adulto |
| ClinicalTrials.gov Identifier: | NCT03455504 |
| Other Study ID Numbers: |
AML1718 2018-000392-33 ( EudraCT Number ) |
| First Posted: | March 6, 2018 Key Record Dates |
| Last Update Posted: | January 10, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Acute myeloid leukemia Venetoclax |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type |
Neoplasms Venetoclax Antineoplastic Agents |