Ignite Creation Date:
2025-12-24 @ 11:51 PM
Ignite Modification Date:
2026-01-02 @ 6:01 PM
Study NCT ID:
NCT04250051
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-01-13
First Post:
2020-01-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Ivosidenib and Combination Chemotherapy for the Treatment of IDH1 Mutant Relapsed or Refractory Acute Myeloid Leukemia
Sponsor:
Northwestern University
Organization:
Study Overview
Official Title:
Phase 1 Trial of Ivosidenib and FLAG Chemotherapy in Relapsed/Refractory IDH1+ Acute Myeloid Leukemia (AML)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of ivosidenib when given together with combination chemotherapy for the treatment of 1DH1 mutant acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). Ivosidenib may stop the growth of cancer cells by blocking the IDH1 mutation and some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate, cytarabine, and filgrastim, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ivosidenib with combination chemotherapy may work better in treating patients with acute myeloid leukemia compared to chemotherapy alone.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) of ivosidenib in combination with fludarabine, cytarabine, plus granulocyte-colony stimulating factor (G-CSF) (FLAG) chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of ivosidenib in combination with FLAG chemotherapy.
II. To determine the rate of complete remission (CR + complete remission with incomplete hematological recovery \[CRi\] + complete remission with incomplete platelet recovery \[CRp\]) with ivosidenib in combination with FLAG chemotherapy.
III. To evaluate the 1 year progression free survival. IV. To evaluate the 1 year overall survival. V. To assess the number of patients that receive allogeneic stem cell transplant after ivosidenib in combination with FLAG chemotherapy.
EXPLORATORY OBJECTIVES:
I. To assess for minimal residual disease negativity by polymerase chain reaction (PCR) for IDH1 mutations after treatment with ivosidenib in combination with FLAG chemotherapy.
II. To assess for minimal residual disease negativity by PCR for IDH1 mutations after 3 cycles of maintenance therapy.
OUTLINE:
INDUCTION: Patients receive filgrastim subcutaneously (SC) once daily (QD) on days 0-6, fludarabine phosphate intravenously (IV) QD over 30 minutes on days 1-5, cytarabine IV QD over 4 hours on days 1-5, and ivosidenib orally (PO) QD on days 7-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive filgrastim SC QD on days 0-5, fludarabine phosphate IV QD over 30 minutes on days 1-4, cytarabine IV QD over 4 hours on days 1-4, and ivosidenib PO QD on days 1-28. Treatment continues for 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every month for up to 1 year.
I. To determine the maximum tolerated dose (MTD) of ivosidenib in combination with fludarabine, cytarabine, plus granulocyte-colony stimulating factor (G-CSF) (FLAG) chemotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile of ivosidenib in combination with FLAG chemotherapy.
II. To determine the rate of complete remission (CR + complete remission with incomplete hematological recovery \[CRi\] + complete remission with incomplete platelet recovery \[CRp\]) with ivosidenib in combination with FLAG chemotherapy.
III. To evaluate the 1 year progression free survival. IV. To evaluate the 1 year overall survival. V. To assess the number of patients that receive allogeneic stem cell transplant after ivosidenib in combination with FLAG chemotherapy.
EXPLORATORY OBJECTIVES:
I. To assess for minimal residual disease negativity by polymerase chain reaction (PCR) for IDH1 mutations after treatment with ivosidenib in combination with FLAG chemotherapy.
II. To assess for minimal residual disease negativity by PCR for IDH1 mutations after 3 cycles of maintenance therapy.
OUTLINE:
INDUCTION: Patients receive filgrastim subcutaneously (SC) once daily (QD) on days 0-6, fludarabine phosphate intravenously (IV) QD over 30 minutes on days 1-5, cytarabine IV QD over 4 hours on days 1-5, and ivosidenib orally (PO) QD on days 7-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Patients receive filgrastim SC QD on days 0-5, fludarabine phosphate IV QD over 30 minutes on days 1-4, cytarabine IV QD over 4 hours on days 1-4, and ivosidenib PO QD on days 1-28. Treatment continues for 28 days for 1 cycle in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every month for up to 1 year.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| STU00210558 | None | CTRP (Clinical Trial Reporting Program) | View | |
| NU 19H05 | OTHER | Northwestern University | View | |
| P30CA060553 | NIH | None | https://reporter.nih.gov/quic… | View |
| NCI-2019-08390 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View |