Overview

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

Status:
Terminated

Trial end date:
2016-08-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Phase 1/Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

M.D. Anderson Cancer Center

Collaborators:

Seagen Inc.
Seattle Genetics, Inc.

Treatments:

Antibodies, Monoclonal
Azacitidine
Brentuximab Vedotin

Criteria

Inclusion Criteria:

1. 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.

2. 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)

3. Age 18 years or older

4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of
5. The following baseline laboratory data: Serum bilirubin (ULN) or ULN AND creatinine clearance >30 ml/min; Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST)
6. 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.

7. 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

8. Patients or their legally authorized representative must provide written informed
consent.

Exclusion Criteria:

1. 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).

2. 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

3. 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.

4. Previous treatment with any anti-CD30 directed therapy

5. 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

6. Patients with uncontrolled active infections (viral, bacterial, and fungal) are not
eligible.

7. Known to be positive for hepatitis B by surface antigen expression

8. Known to have active hepatitis C infection (positive by polymerase chain reaction or
on antiviral therapy for hepatitis C within the last 6 months)

9. Preexisting grade >/=2 peripheral neuropathy

10. Patients with uncontrolled diabetes mellitus

11. Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational
agents.

12. 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

13. Females who are pregnant or lactating

14. Known hypersensitivity to any excipient contained in the drug formulation of
brentuximab vedotin

15. History of progressive multifocal leukoencephalopathy (PML)