Brentuximab Vedotin + Re-induction Chemotherapy for AML

NCT01830777 | Completed Phase 1 DMC

• 1 other identifier: 13-040
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is a Phase I clinical trial. Phase I trials test the safety of an investigational drug or combination of drugs. These trials also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the combination of drugs is still being studied and that research doctors are trying to find out more about it. As part of this research study, patients will be administered brentuximab vedotin in combination with a conventional re-induction chemotherapy regimen called MEC, which consists of the chemotherapy drugs mitoxantrone, etoposide, and cytarabine. Brentuximab vedotin has not been approved by the FDA for the patient's cancer. However, brentuximab targets a protein on tumors called CD30, and it is approved for other cancers which express CD30, and these include Hodgkin lymphoma. This means that the FDA has not approved giving brentuximab in conjunction with MEC for use in people, including people with this type of malignancy, acute myeloid leukemia (AML). Mitoxantrone, etoposide and cytarabine are chemotherapy agents that are commonly used to treat individuals with relapsed AML. Brentuximab is an antibody-drug conjugate (ADC), which is the combination of an antibody (a protein that binds to cells) and a drug. Brentuximab vedotin works by using the antibody portion to enter into CD30-positive cells and then releasing the drug portion, which attempts to destroy the cell. Brentuximab vedotin has been used in laboratory and other research studies and information from those studies suggest that brentuximab vedotin may slow down the spread of cancers which express CD30. Some AML cell express CD30, so investigators hope that brentuximab vedotin will help with this type of AML. The primary purpose of this research study is to determine the highest dose that Brentuximab vedotin can safely be given with MEC without severe or unmanageable side effects. The dose identified in this study will be used in future research studies.

Conditions

Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (1)

• Define Maximum Tolerated Dose of Brentuximab Vedotin + MEC

  The primary objective of this trial is to define the maximum tolerated dose (MTD) of the CD30 antibody drug conjugate brentuximab vedotin in combination with MEC re-induction chemotherapy in patients with relapsed acute myeloid leukemia and expression of CD30.

  2 years

Secondary Outcomes (6)

• Detect and Categorize Incidences of Drug Related Toxicities

  2 years

• Determine Response Rate

  2 years

• Measure Overall Survival

  2 years

• Assess CD30 Status by Flow Cytometry

  2 years

• Assess Pharmacodynamic Effects of CD30 Targeted Therapy

  2 years

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Brentuximab Vedotin + MEC

Drug: Brentuximab Vedotin; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Interventions

Brentuximab Vedotin DRUG

Intravenously on Day 1 during re-induction therapy. Intravenously every 21 days during maintenance therapy

Experimental Arm

Mitoxantrone DRUG

Intravenously on Days 3-7 of re-induction therapy.

Experimental Arm

Etoposide DRUG

Intravenously on Days 3-7 of re-induction therapy.

Experimental Arm

Cytarabine DRUG

Intravenously on Days 3-7 of re-induction therapy.

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed, relapsed acute myelogenous leukemia following a remission duration of at least 3 months
• CD30 expressing AML
• Willing to use acceptable method of contraception

You may not qualify if:

• Have received systemic antineoplastic therapy, including radiotherapy within 14 days of study treatment
• Pregnant or breastfeeding
• Diagnosis of acute promyelocytic leukemia
• Refractory acute myeloid leukemia
• History of a different malignancy except if disease free for at least 5 years and at low risk of remission or one of the following within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin
• Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy
• Uncontrolled intercurrent illness
• HIV positive on combination antiretroviral therapy
• Diagnosis of active hepatitis B or C
• Current or history of congestive heart failure NYHA class 3 or 4
• Current or history of ventricular or life-threatening arrythmias or diagnosis of long-QT syndrome
• Systemic infection requiring IV antibiotic therapy within 7 days before first dose of study drug

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Narayan R, Blonquist TM, Emadi A, Hasserjian RP, Burke M, Lescinskas C, Neuberg DS, Brunner AM, Hobbs G, Hock H, McAfee SL, Chen YB, Attar E, Graubert TA, Bertoli C, Moran JA, Bergeron MK, Foster JE, Ramos AY, Som TT, Vartanian MK, Story JL, McGregor K, Macrae M, Behnan T, Wey MC, Rae J, Preffer FI, Lesho P, Duong VH, Mann ML, Ballen KK, Connolly C, Amrein PC, Fathi AT. A phase 1 study of the antibody-drug conjugate brentuximab vedotin with re-induction chemotherapy in patients with CD30-expressing relapsed/refractory acute myeloid leukemia. Cancer. 2020 Mar 15;126(6):1264-1273. doi: 10.1002/cncr.32657. Epub 2019 Dec 20.

  PMID: 31860140 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Brentuximab Vedotin; Mitoxantrone; Etoposide; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Amir Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 12, 2013
• Study Start: May 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: May 1, 2019
• Last Updated: April 14, 2020

Record last verified: 2020-04

Locations

US (1)