What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) that target CD123-positive cells include IMGN632, azacitidine, and venetoclax. IMGN632, an antibody-drug conjugate, can cause side effects such as infusion-related reactions, fatigue, and cytopenias. Azacitidine, a hypomethylating agent, often leads to side effects like nausea, vomiting, diarrhea, and myelosuppression. Venetoclax, a BCL-2 inhibitor, is associated with neutropenia, infections, and gastrointestinal symptoms. These treatments aim to target and eliminate leukemic cells but can also impact normal cells, leading to these adverse effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Acute Myeloid Leukemia (AML). Notably, azacitidine and decitabine are hypomethylating agents that have shown superior survival and response rates compared to supportive care in AML patients. Venetoclax, often used in combination with azacitidine or decitabine, has also been approved for newly diagnosed AML in patients ineligible for intensive chemotherapy. While specific FDA approvals for CD123-targeting drugs like IMGN632 are not detailed in the provided context, these hypomethylating agents and combination therapies represent significant advancements in AML treatment.

What other types of research exist?

Promising novel alternatives to IMGN632 for CD123-positive AML include next-generation antibody-drug conjugates (ADCs) targeting CD33 and CD123, which have shown improved safety and therapeutic index in preclinical models. Additionally, the human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 combined with Auger electron-emitting anti-CD123 radioimmunoconjugates has demonstrated potential in radiosensitizing AML cells.

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Antibody-Drug Conjugate

IMGN632 + Venetoclax/Azacitidine for Acute Myeloid Leukemia

Phase 1 & 2

Waitlist Available

Research Sponsored by ImmunoGen, Inc.

Eligibility Criteria Checklist

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

Must have

Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry [IHC]).

An estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2 or creatinine clearance of > 30 mL/min.

Must not have

Patients with a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver.

Prior known hypersensitivity reactions to monoclonal antibodies (≥ Grade 3).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 20 months

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial tests a new drug, IMGN632, combined with other drugs to treat patients with a specific type of leukemia. It aims to see if this combination can effectively target and kill cancer cells while stopping them from growing.

Who is the study for?

Adults with CD123-positive Acute Myeloid Leukemia (AML) who have either relapsed or are treatment-naive can join this trial. They must be fit for experimental therapy, not have acute promyelocytic leukemia, and should not have had certain prior treatments. Participants need normal organ function and controlled previous cancers if any.

What is being tested?

The safety and effectiveness of IMGN632 alone or combined with azacitidine and/or venetoclax in treating AML are being tested. This study is open-label, meaning everyone knows which treatment they're getting, and it's happening at multiple centers.

What are the potential side effects?

Possible side effects include reactions related to the immune system due to monoclonal antibodies like IMGN632, liver issues from azacitidine or venetoclax, blood count changes, fatigue, digestive problems, and potential increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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My AML is CD123-positive as confirmed by tests.

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My kidney function, measured by eGFR or creatinine clearance, is above 30 mL/min.

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I had a bone marrow transplant over 4 months ago, have no severe graft disease, and haven't been on immunosuppressants for 2 weeks.

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I have been diagnosed with AML, not including acute promyelocytic leukemia.

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I am a woman who can have children and agree to use birth control during and 7 months after the study.

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I am 18 years old or older.

Exclusion Criteria

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

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I have had a liver condition called sinusoidal obstruction syndrome.

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I have had a severe allergic reaction to monoclonal antibodies.

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I am not allergic to IMGN632, azacitidine, or venetoclax.

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I haven't had a heart attack in the last 6 months and don't have severe heart issues.

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I am not pregnant or breastfeeding.

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I have been treated with IMGN632 before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 20 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 20 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 20 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Minimal Residual Disease Levels

Preliminary antileukemia activity

Safety and Tolerability

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Regimen D (Closed to Enrollment)Experimental Treatment1 Intervention

IMGN632, administered intravenously on Day 1 of a 21 day cycle at 0.045 mg/kg, as a monotherapy for Fit and Unfit MRD+ patients.

Group II: Regimen C - Frontline & Relapsed / Refractory (Closed to Enrollment)Experimental Treatment3 Interventions

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg or 0.045 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 35-75 mg/m2 given for Days 1 to 7 of a 28 day cycle and venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on Day 3 up to Day 28 of a 28 day cycle. Alternate schedules with reduced venetoclax administration or reduced azacitidine dose or administration may be explored.

Group III: Regimen B (Closed to Enrollment)Experimental Treatment2 Interventions

IMGN632, administered intravenously on Day 7 of a 21 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with venetoclax, administered orally daily at 100 mg on Day 1, 200mg on Day 2, and 400 mg on the day 3 up to Day 21 of a 21 day cycle. Alternate schedules with reduced venetoclax administration may be explored.

Group IV: Regimen A (Closed to Enrollment)Experimental Treatment2 Interventions

IMGN632, administered intravenously on Day 7 of a 28 day cycle at 0.015 mg/kg, 0.045 mg/kg, or 0.09 mg/kg, in combination with azacitidine, administered subcutaneously or intravenously daily at 75 mg/m2 on Days 1 to 7 of a 28 day cycle. Cycle 1 azacitidine dose in subsequent cohorts may be reduced.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Decitabine

FDA approved

Venetoclax

FDA approved

0 / 12Eligibility 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 therapies, and immunotherapies. Chemotherapy agents like cytarabine and daunorubicin work by interfering with DNA replication, leading to cell death. Targeted therapies, such as FLT3 inhibitors, specifically inhibit mutant proteins that drive leukemia cell proliferation. Immunotherapies, including monoclonal antibodies like IMGN632, target specific antigens such as CD123 on leukemia cells, delivering cytotoxic agents directly to the cancer cells. These mechanisms are crucial for AML patients as they offer more precise and effective treatment options, potentially reducing side effects and improving outcomes by directly targeting the malignant cells.

Emerging Epigenetic Therapeutic Targets in Acute Myeloid Leukemia.Molecular targeting in acute myeloid leukemia.Childhood acute myeloid leukaemia.

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Who is running the clinical trial?

ImmunoGen, Inc.Lead Sponsor

32 Previous Clinical Trials

3,607 Total Patients Enrolled

Jazz PharmaceuticalsIndustry Sponsor

249 Previous Clinical Trials

34,626 Total Patients Enrolled

Patrick Zweidler-McKay, MD, PhDStudy DirectorImmunoGen, Inc.

1 Previous Clinical Trials

264 Total Patients Enrolled

Media Library

IMGN632 (Antibody-Drug Conjugate) Clinical Trial Eligibility Overview. Trial Name: NCT04086264 — Phase 1 & 2

$Acute Myeloid Leukemia Research Study Groups: Regimen D (Closed to Enrollment), Regimen B (Closed to Enrollment), Regimen C - Frontline & Relapsed / Refractory (Closed to Enrollment), Regimen A (Closed to Enrollment)$