Phase I/II - Brentuximab/5-Azacytidine in Acute Myeloid Leukemia (AML)

NCT02096042 | Terminated Phase 1 Results

• 2 other identifiers: 2013-0706NCI-2014-01114
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical research study is made up of 3 phases: a Pilot Phase, Phase 1, and Phase 2. The goal of the Pilot Phase is to learn how safe it is to give the study drug brentuximab vedotin to patients with AML. The goal of Phase 1 is to learn more about the safety of the combination of brentuximab vedotin with azacytidine. The goal of Phase 2 is to learn if the combination of brentuximab vedotin and azacytidine can help to control AML.

Conditions

Leukemia

Keywords

Leukemia; Acute Myeloid Leukemia; AML; CD30-Positive; Relapsed; Refractory; Brentuximab Vedotin; SGN-35; Adcetris; 5-Azacytidine; Azacytidine; Azacitidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Brentuximab Vedotin in Combination With 5-Azacytidine

  MTD defined as maximum dose at which \<33% of patients experience a dose-limiting toxicity (DLT) during cycle 1.

  After 1, 28 day cycle

• Overall Response Rate

  Response defined as number of participants with complete response (CR), CR with incomplete platelet recovery (CRp), CR with insufficient hematological recovery (CRi) or partial remission (PR).

  Response assessed after four 28-day cycles, up to 120 days

Study Arms (2)

Brentuximab Vedotin

EXPERIMENTAL

Pilot Phase: Starting dose of Brentuximab Vedotin 1.2 mg/kg intravenous (IV) infusion over approximately 30 minutes on days 1, 8, and 15 of each 28-day cycle (+/- 3 days).

Drug: Brentuximab Vedotin

Brentuximab Vedotin + 5-Azacytidine

EXPERIMENTAL

Phase I Dose-Escalation Phase: Starting dose of Brentuximab Vedotin 1.0 mg/kg IV (starting dose level 1), or one-dose level lower than the established MTD if the pilot portion of the study establishes a lower MTD, infusion over approximately 30 minutes on days 1, 8, and 15 of each 28-day cycle. All patients receive 5-azacytidine at 75 mg/m2/day by vein or subcutaneously on days 1-7 every 28 days. Phase II Dose-Expansion Phase: Patients receive Brentuximab Vedotin at MTD from dose-escalation phase by vein on Days 1, 8, and 15 of each 28-day cycle. Patients receive 5-Azacytidine at 75 mg/m2/day by vein or subcutaneously on days 1-7 every 28 days. Patients can receive up to a total of 12 cycles of treatment (weekly + monthly combined).

Drug: Brentuximab Vedotin; Drug: 5-Azacytidine

Interventions

Brentuximab Vedotin DRUG

Pilot Phase: Starting dose of Brentuximab Vedotin 1.2 mg/kg intravenous (IV) infusion over approximately 30 minutes on days 1, 8, and 15 of each 28-day cycle. Phase I Dose-Escalation Phase: Starting dose of Brentuximab Vedotin 1.0 mg/kg IV (starting dose level 1), or one-dose level lower than the established MTD if the pilot portion of the study establishes a lower MTD, infusion over approximately 30 minutes on days 1, 8, and 15 of each 28-day cycle. Phase II Dose-Expansion Phase: Patients receive Brentuximab Vedotin at MTD from dose-escalation phase by vein on Days 1, 8, and 15 of each 28-day cycle.

Also known as: SGN-35, Adcetris

Brentuximab Vedotin; Brentuximab Vedotin + 5-Azacytidine

5-Azacytidine DRUG

Phase I Dose-Escalation Phase and Phase II Dose-Expansion Phase: 5-Azacytidine at 75 mg/m2/day by vein or subcutaneously on days 1-7 every 28 days.

Also known as: Azacytidine, Azacitidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Brentuximab Vedotin + 5-Azacytidine

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed AML, other than acute promyelocytic leukemia, as defined by the 2008 World Health Organization (WHO) criteria that is relapsed or refractory to standard chemotherapy. Note: Newly-diagnosed AML patients who are 60 years or older and are not candidates for or have refused standard chemotherapy are also eligible for this trial.
• AML blasts must express CD30 (\>/=10% expression as assessed by flow-cytometry or 2+ expression by immunohistochemistry) (whenever possible CD30 expression will be assessed by both methods)
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of \</=3
• The following baseline laboratory data: Serum bilirubin \</=1.5 x upper limit of normal (ULN) or \</= 3 x ULN for patients with Gilbert's disease; Serum creatinine \</=1.5 x ULN AND creatinine clearance \>30 ml/min; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</=3 x ULN
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the first dose of brentuximab vedotin and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
• Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
• Patients or their legally authorized representative must provide written informed consent.

You may not qualify if:

• History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to their first dose of brentuximab vedotin
• Evidence of active cerebral/meningeal disease. Patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration.
• Previous treatment with any anti-CD30 directed therapy
• Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: \<100 days from allogeneic SCT, Acute or chronic graft-versus-host disease (GvHD), or Receiving immunosuppressive therapy as treatment for or prophylaxis against GvHD within the last 7 days
• Patients with uncontrolled active infections (viral, bacterial, and fungal) are not eligible.
• Known to be positive for hepatitis B by surface antigen expression
• Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months)
• Preexisting grade \>/=2 peripheral neuropathy
• Patients with uncontrolled diabetes mellitus
• Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents.
• Chemotherapy (except hydroxyurea or emergent use of single-agent cytarabine for cytoreduction), radiotherapy, biologics, and/or other treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug, unless progressive disease is documented. NOTE: Hydroxyurea will be allowed during the first cycle of treatment
• Females who are pregnant or lactating
• Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin
• History of progressive multifocal leukoencephalopathy (PML)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Seagen Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Recurrence

Interventions

Brentuximab Vedotin; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Nitin Jain, MD/Assistant Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Nitin Jain, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 26, 2014
• Study Start: April 1, 2014
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: October 10, 2023
• Results First Posted: September 5, 2017

Record last verified: 2023-10

Locations

US (1)