NCT04250051

Ivosidenib and Combination Chemotherapy for the Treatment of IDH1 Mutant Relapsed or Refractory Acute Myeloid Leukemia

Phase 1 Trial of Ivosidenib and FLAG Chemotherapy in Relapsed/Refractory IDH1+ Acute Myeloid Leukemia (AML)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Syndrome
• Recurrent Myeloproliferative Neoplasm
• Refractory Acute Myeloid Leukemia
• Refractory Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV
BIOLOGICAL	Filgrastim	Given SC
DRUG	Fludarabine	Given IV
DRUG	Fludarabine Phosphate	Given IV
DRUG	Ivosidenib	Given PO

Timeline

• Start date: 2020-12-21
• Primary completion: 2025-01-08
• Completion: 2028-12-01
• First posted: 2020-01-31
• Last updated: 2025-01-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study