What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) often involve chemotherapy, monoclonal antibodies, and radiation therapy. Chemotherapy drugs like fludarabine and melphalan can cause side effects such as leukopenia, thrombocytopenia, anemia, infections, and increased transaminases. Monoclonal antibodies targeting specific cancer cells may lead to infusion reactions, fatigue, and immunosuppression. Total marrow and lymphoid irradiation (TMLI) can result in side effects like nausea, fatigue, and increased risk of infections. Combining these treatments aims to improve outcomes but also increases the potential for cumulative side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML), including monoclonal antibodies and targeted therapies. For instance, gemtuzumab ozogamicin, an antibody-drug conjugate targeting CD33, has been approved for newly diagnosed and relapsed AML. Additionally, hypomethylating agents like azacitidine and decitabine are commonly used for AML treatment. While specific FDA approvals for treatments exactly like 90Y-DOTA-anti-CD25 basiliximab are not detailed, the use of monoclonal antibodies and targeted therapies in AML is well-established.

What other types of research exist?

Promising novel alternatives for AML treatment include: 1) Actinium-225-lintuzumab, an anti-CD33 antibody conjugated to actinium-225, which has shown safety and biological activity in early trials. 2) Venetoclax combined with hypomethylating agents (HMAs) like azacitidine or decitabine, which has demonstrated improved outcomes in AML patients. 3) IDH inhibitors such as ivosidenib for IDH1-mutated AML, which can induce durable remissions. 4) FLT3 inhibitors like gilteritinib, especially in combination with HMAs, which have shown higher overall response rates. These alternatives represent targeted and combination therapies that are currently under investigation or have shown promising results in clinical trials.

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Radioactive Agent

Radioimmunotherapy + Chemotherapy for Leukemia

Phase 1

Recruiting

Led By Jeffrey Y Wong

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Karnofsky performance status >= 70

Myelodysplastic syndrome in high-intermediate (int-2) and high-risk categories

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of therapy up to 2 years post-transplant

Awards & highlights

Study Summary

This trial is to find out if 90Y-DOTA-anti-CD25 basiliximab, given with fludarabine, melphalan, and total marrow and lymphoid irradiation, is an effective treatment for high-risk acute leukemia or myelodysplastic syndrome.

Who is the study for?

This trial is for adults with high-risk acute leukemia or myelodysplastic syndrome who are not candidates for intensive treatment due to age or comorbidities. Participants must have CD25 positive cancer cells, adequate organ function, and agree to birth control measures. Those with more than three prior treatments, uncontrolled infections, recent intensive therapies, or unable to comply with study procedures are excluded.Check my eligibility

What is being tested?

The trial tests a combination of the radioactive antibody 90Y-DOTA-anti-CD25 basiliximab with chemotherapy drugs fludarabine and melphalan, plus total marrow and lymphoid irradiation (TMLI). It aims to determine the best dose and assess potential benefits and side effects in preparation for stem cell transplantation.See study design

What are the potential side effects?

Potential side effects include reactions related to radiation exposure such as fatigue and nausea; immune responses from the monoclonal antibody; complications from chemotherapy like low blood counts leading to infection risk; organ inflammation; allergic reactions; and infertility risks.

Eligibility Criteria

Inclusion Criteria

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

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I am able to care for myself but may not be able to do active work.

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My condition is a high-risk type of bone marrow disorder.

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My blood cancer diagnosis is confirmed and tests positive for CD25.

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My AML is classified as high or intermediate risk, except FLT3-NPM1+.

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My cancer is in remission but still shows minimal signs under detailed tests.

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My leukemia has specific genetic features or high white blood cell counts.

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My cancer is in remission but still shows signs of disease on a cellular level.

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I have acute myelogenous leukemia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of therapy up to 2 years post-transplant

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of therapy up to 2 years post-transplant

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of therapy up to 2 years post-transplant for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Incidence of toxicity

Maximum tolerated dose/recommended phase II dose of 90Y-DOTA-antiradioimmunotherapy

Secondary outcome measures

Complete remission (CR) proportion at day +30

Event-free survival

Graft versus host disease and relapse free survival

+8 more

Side effects data

From 2019 Phase 2 trial • 77 Patients • NCT01251575

Hypoxia

Febrile neutropenia

Acute kidney injury

Blood bilirubin increased

Diarrhea

Creatinine increased

Sepsis

Hypotension

Left ventricular systolic dysfunction

Bronchopulmonary hemorrhage

Chronic kidney disease

Thromboembolic event

Lung infection

Atrial fibrillation

Atrial flutter

Hemolysis

Hemolytic uremic syndrome

Ejection fraction decreased

Encephalitis infection

Gastric hemorrhage

Gastritis

Heart failure

Mucositis oral

Multi-organ failure

Myalgia

Pleural effusion

Respiratory failure

Small intestine infection

Syncope

Treatment related secondary malignancy

Typhlitis

Fever

Paroxysmal atrial tachycardia

Ascites

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (Fludarabine, Transplant, Immunosuppression)

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (90Y-basiliximab, fludarabine, melphalan, TMLI)Experimental Treatment9 Interventions

Patients receive cold basiliximab IV, 111In-DOTA-anti-CD25 basiliximab IV, and 90Y-DOTA-anti-CD25 basiliximab IV on day -15. Patients also receive palifermin IV on days -11 to -9, fludarabine phosphate IV on days -4 to -2, melphalan IV on day -2, and undergo TMLI on days -8 to -5 in the absence of disease progression or unacceptable toxicity. Patients then undergo AHSCT on day 0.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Total Marrow Irradiation

2014

Completed Phase 1

~20

Total Lymphoid Irradiation

2008

Completed Phase 3

~160

Palifermin

2006

Completed Phase 3

~1200

Basiliximab

2006

Completed Phase 4

~4130

Melphalan

2008

Completed Phase 3

~1500

Allogeneic Hematopoietic Stem Cell Transplantation

2012

Completed Phase 2

~1200

Fludarabine Phosphate

1997

Completed Phase 3

~2390

0 / 8Eligibility 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

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy, targeted therapy, and monoclonal antibodies. Chemotherapy drugs like fludarabine and melphalan work by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, such as those inhibiting specific mutations (e.g., FLT3 inhibitors), block the signaling pathways that promote cancer cell growth. Monoclonal antibodies, like 90Y-DOTA-anti-CD25 basiliximab, specifically target cancer cells expressing certain markers (e.g., CD25) and deliver cytotoxic agents directly to them, minimizing damage to healthy cells. These mechanisms are crucial for AML patients as they offer more precise and effective treatment options, potentially improving outcomes and reducing side effects.

Emerging Targeted Therapy for Specific Genomic Abnormalities in Acute Myeloid Leukemia.Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia.Small molecule inhibition of cAMP response element binding protein in human acute myeloid leukemia cells.