What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include hypomethylating agents like Azacitidine and monoclonal antibodies such as SEA-CD70. Azacitidine is associated with side effects such as cytopenias (low blood cell counts), febrile neutropenia (fever with low white blood cell count), thrombocytopenia (low platelet count), pneumonia, and anemia. Monoclonal antibodies like SEA-CD70 may cause infusion-related reactions, including fever, chills, and fatigue, as well as potential immunosuppression leading to increased infection risk. Both treatment types require careful monitoring and supportive care to manage these side effects.

What prior FDA approvals exist?

For the treatment of Acute Myeloid Leukemia (AML), the FDA has approved several drugs that are similar to those being studied in the SEA-CD70 trial. Azacitidine, a DNA methyltransferase inhibitor, is already FDA-approved for AML and is known for its ability to induce hematologic responses and improve survival rates. Other hypomethylating agents like Decitabine have also been approved for AML. While there are no FDA-approved monoclonal antibodies specifically targeting CD70 for AML, other monoclonal antibodies and targeted therapies, such as Gemtuzumab ozogamicin (an anti-CD33 antibody-drug conjugate), have been approved for specific AML subtypes. These approvals highlight the ongoing efforts to develop targeted therapies for AML.

What other types of research exist?

Promising novel alternatives for AML treatment include: 1) Gemtuzumab ozogamicin, an antibody-drug conjugate targeting CD33, which has shown efficacy in relapsed AML. 2) Anti-SAIL antibody-drug conjugates (ADCs) like 7-1C and 67-7A, which have demonstrated significant tumor growth inhibition in AML cell lines. 3) Venetoclax, a BCL-2 inhibitor, in combination with hypomethylating agents (HMAs) like decitabine or azacitidine, which has shown improved outcomes in AML patients. 4) Targeted alpha-particle immunotherapy using (225)Ac-lintuzumab, which has shown antileukemic activity in early trials. These alternatives offer different mechanisms of action and potential benefits for AML patients.

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Monoclonal Antibodies

SEA-CD70 for Myelodysplastic Syndrome and Acute Myeloid Leukemia

Phase 1

Recruiting

Research Sponsored by Seagen Inc.

Eligibility Criteria Checklist

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

Must have

Intolerance of HMA (Grade 3 or higher non-hematologic toxicity leading to treatment discontinuation).

MDS that is relapsed or refractory and must not have other therapeutic options known to provide clinical benefit in MDS available.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug, SEA-CD70, alone and with azacitidine, to see if it is safe and works for adults with certain blood cancers that haven't responded to other treatments. The study will determine the best dose and check for side effects. Azacitidine is a treatment that improves survival, reduces the need for transfusions, and lowers the risk of progression to acute myeloid leukemia in patients with higher risk myelodysplastic syndromes.

Who is the study for?

This trial is for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Participants must have relapsed after partial remission or shown no response to previous treatments like azacitidine. They should be in good physical condition, with an ECOG performance status of 0-1, and not have other treatment options available.

What is being tested?

The study tests SEA-CD70 alone and combined with azacitidine to determine the safe dosage levels and effectiveness against MDS and AML. It's divided into six parts, each aiming to establish safety profiles and dosages for different patient groups within these conditions.

What are the potential side effects?

Potential side effects are not specified but generally include any unintended effects besides treating cancer. These could range from mild reactions at the injection site to more serious systemic responses.

Eligibility Criteria

Inclusion Criteria

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

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I had a severe reaction to HMA treatment and had to stop it.

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My MDS has returned or is not responding to treatment, and I have no other known beneficial treatment options.

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My treatment with azacitidine or decitabine for at least 6 or 4 cycles, respectively, did not work.

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My condition worsened after starting HMA therapy.

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I am fully active or can carry out light work.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 4 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

Number of participants with a dose-limiting toxicity (DLT) at each dose level (Parts A and D only)

Number of participants with adverse events (AEs)

Number of participants with laboratory abnormalities

Secondary study objectives

AUC - Area under the plasma concentration-time curve

Cmax - Maximum observed plasma concentration

Complete remission (CR) Rate and complete remission equivalent (CReq) rate

+17 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Part FExperimental Treatment2 Interventions

SEA-CD70 + azacitidine expansion cohort in relapsed/refractory MDS or MDS/AML

Group II: Part EExperimental Treatment2 Interventions

SEA-CD70 + azacitidine expansion cohort in previously untreated higher-risk MDS or MDS/AML

Group III: Part DExperimental Treatment2 Interventions

SEA-CD70 + azacitidine dose-finding/dose optimization cohorts in relapsed/refractory MDS or MDS/AML, and previously untreated higher-risk MDS or MDS/AML

Group IV: Part CExperimental Treatment1 Intervention

SEA-CD70 expansion cohort in relapsed/refractory AML

Group V: Part BExperimental Treatment1 Intervention

SEA-CD70 expansion cohort in relapsed/refractory (HMA-failure) MDS

Group VI: Part AExperimental Treatment1 Intervention

SEA-CD70 dose escalation cohort in relapsed/refractory (HMA-failure) MDS

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

azacitidine

2005

Completed Phase 3

~1730

0 / 5Eligibility 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

Monoclonal antibodies like SEA-CD70 target specific antigens on cancer cells, such as CD70, leading to their destruction by the immune system, which helps minimize damage to healthy cells. Azacitidine, a DNA methyltransferase inhibitor, incorporates into DNA and RNA, causing hypomethylation and reactivation of tumor suppressor genes, leading to cancer cell differentiation and apoptosis. These mechanisms are important for AML patients as they offer targeted and potentially less toxic treatment options, improving outcomes and quality of life.

Epigenetic deregulation in myeloid malignancies.Role of epigenetic in leukemia: From mechanism to therapy.Epigenetic therapy: azacytidine and decitabine in acute myeloid leukemia.