What side effects are associated with this type of intervention?

Common treatments for Acute Myelogenous Leukemia (AML) include enzyme inhibitors like Sorafenib and chemotherapy agents such as Busulfan and Fludarabine. Sorafenib can cause fatigue, nausea, diarrhea, and skin reactions. Busulfan is associated with myelosuppression, mucositis, and potential pulmonary toxicity. Fludarabine may lead to immunosuppression, increased infection risk, and neurotoxicity. Combining these treatments can enhance efficacy but also increases the risk of compounded side effects.

What prior FDA approvals exist?

Several FDA-approved treatments for Acute Myelogenous Leukemia (AML) involve enzyme inhibition and chemotherapy. Venetoclax, an oral BCL-2 inhibitor, is often used in combination with hypomethylating agents like azacitidine or decitabine. Ivosidenib and Enasidenib are IDH1 and IDH2 inhibitors, respectively, approved for AML with specific mutations. Chemotherapy regimens such as cytarabine and daunorubicin (7+3 regimen) are standard treatments. Additionally, midostaurin, a FLT3 inhibitor, is approved for use with standard chemotherapy in FLT3-mutated AML. These treatments reflect the combination of targeted enzyme inhibition and traditional chemotherapy approaches.

What other types of research exist?

Promising novel alternatives for AML treatment in 2024 include: 1) Enasidenib and Ivosidenib for IDH2 and IDH1 mutations, respectively. 2) Gilteritinib for FLT3 mutations. 3) Venetoclax in combination with hypomethylating agents or low-dose cytarabine. 4) Nintedanib combined with low-dose cytarabine, particularly for elderly patients ineligible for intensive chemotherapy.

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Alkylating Agent

Sorafenib + Chemotherapy for Acute Myeloid Leukemia

Phase 1 & 2

Waitlist Available

Led By Uday R Popat

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Human leukocyte antigen (HLA)-identical sibling or 8/8 matched unrelated donor available

Age between 18 and 70 years

Must not have

Acute myeloid leukemia in first complete molecular remission and favorable risk disease as defined by presence of t(8:21) or inv (16)

Uncontrolled hypertension (systolic pressure greater than 140 mm Hg or diastolic pressure greater than 90 mm Hg [NCI-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0] on repeated measurement) despite optimal medical management

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the best dose of sorafenib combined with busulfan and fludarabine for patients with hard-to-treat acute myeloid leukemia. Sorafenib blocks enzymes needed for cancer growth, while busulfan and fludarabine kill or stop the spread of cancer cells. Sorafenib has shown potential in early studies for treating acute myeloid leukemia.

Who is the study for?

Adults aged 18-70 with recurrent or unresponsive acute myeloid leukemia, suitable for donor stem cell transplant. Must have a matched sibling or unrelated donor, normal organ function tests, and agree to contraception. Excludes those with certain heart conditions, bleeding disorders, other cancers within 3 years (except some skin/bladder cancers), major surgery within the last month, and inability to take oral medication.

What is being tested?

The trial is testing the effectiveness of sorafenib combined with busulfan and fludarabine in patients undergoing stem cell transplants for acute myeloid leukemia that has returned or is treatment-resistant. It aims to find the best dose of sorafenib that can block cancer growth when used alongside chemotherapy drugs.

What are the potential side effects?

Potential side effects include risks associated with bone marrow transplantation like infection and graft-versus-host disease. Sorafenib may cause rash, diarrhea, high blood pressure; chemotherapy can lead to nausea, fatigue, mouth sores.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a perfect match donor for my transplant.

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I am between 18 and 70 years old.

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I have acute myeloid leukemia, regardless of flt3 status.

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I can swallow and keep down pills.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My leukemia is in its first full remission and is considered low risk.

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My blood pressure is high despite taking medication.

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I do not have serious heart problems like recent heart attacks or unstable angina.

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I have a wound, ulcer, or bone fracture that is not healing.

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I have not had serious lung bleeding or any other severe bleeding in the last month.

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I haven't taken strong medication like phenytoin or St. John's wort in the last 28 days.

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I am not pregnant or breast-feeding.

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I can follow the study plan and attend all required check-ups.

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I have previously been treated with inotuzumab or gemtuzumab.

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I have had an organ transplant.

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I have a condition that affects how my body absorbs nutrients.

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I am on blood thinners like warfarin or heparin.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD) as defined by toxicity (Phase I)

Progression-free survival (PFS) (Phase II)

Secondary study objectives

Graft failure

Incidence of acute and chronic graft versus host disease graded according to National Cancer Institute CTCAE version 4.0

Non-relapse mortality rate

+2 more

Side effects data

From 2020 Phase 2 trial • 40 Patients • NCT01900002

12%

AST increase

12%

Hypertension

Hyponatremia

Fatigue

ALT increase

Vomiting

Nausea

Dizziness

Diarrhea

Hypophosphatemia

Mucositis

Encephalopathy

Weight Loss

Hypertenstion

Duodenal Ulcer

Sepsis

Acute Renal Failure

Hypotension

Hematuria

Hepatic Hemorrhage

Urinary Retention

Dyspnea

Weakness

Abdominal Pain

Rectal Bleed

Palmar-Planta Erythrodysesthesia

Thrombocytopenia

Hyperbilirubinemia

Proteinuria

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Sorafenib Tosylate, TheraSphere)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (sorafenib, busulfan, fludarabine, HSCT)Experimental Treatment8 Interventions

PRE-STEM CELL INFUSION: Patients receive sorafenib orally PO QD or BID on days -24 to -5, busulfan IV over 3 hours on days -20 and -13 and -6 and -3, and fludarabine IV over 1 hour on days -6 to -3 in the absence of disease progression or unacceptable toxicity. STEM CELL INFUSION: Patients receive allogeneic HSCT IV in the absence of disease progression or unacceptable toxicity. POST-STEM CELL INFUSION: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4, tacrolimus PO BID beginning day 5 for about 50 days, filgrastim SC on day 7 and sorafenib PO BID beginning between days +30 and +120 for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients with matched unrelated donor receive mycophenolate mofetil PO TID or IV over 2 hours TID beginning on day 5 for up to 90 days for longer.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tacrolimus

2019

Completed Phase 4

~5510

Cyclophosphamide

2010

Completed Phase 4

~2310

Filgrastim

2000

Completed Phase 3

~3690

Fludarabine

2012

Completed Phase 4

~1860

Mycophenolate Mofetil

1997

Completed Phase 4

~2380

Sorafenib

2014

Completed Phase 3

~2340

Allogeneic Hematopoietic Stem Cell Transplantation

2012

Completed Phase 2

~1240

Busulfan

2008

Completed Phase 4

~1710

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Acute Myelogenous Leukemia (AML) include enzyme inhibitors and chemotherapeutic agents. Sorafenib, a tyrosine kinase inhibitor, blocks enzymes necessary for cancer cell growth and proliferation. Chemotherapeutic agents like Busulfan and Fludarabine damage the DNA of cancer cells, preventing their replication and leading to cell death. These mechanisms are vital for AML patients as they target the disease at a molecular level, offering potential pathways for remission and long-term disease control.

New therapeutic approaches to acute myeloid leukemia.Drug therapy for acute myeloid leukemia.