Clinical trial NCT02096042
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
Sponsor: M.D. Anderson Cancer Center
Start date: 2014-04-01; Completion date: 2016-08-01
Enrollment: 1 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Detailed description:
Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 3 groups of 3-6 participants will be enrolled in the Pilot Phase, up to 3 groups of 3-6 participants will be enrolled in Phase I of the study, and up to 25 participants will be enrolled in Phase II.

If you are enrolled in the Pilot Phase, the dose of brentuximab vedotin you receive will depend on when you joined this study. The first group of participants will receive the highest dose level of brentuximab vedotin. If intolerable side effects are seen, up to 2 more groups will be enrolled and will receive a lower dose of brentuximab vedotin than the group before it. If intolerable side effects are not seen, the next phase of the study will begin.

If you are enrolled in Phase I, the dose of brentuximab vedotin you receive will depend on when you joined this study. The first group of participants will receive a lower dose level of brentuximab vedotin than the highest one that was tolerated in the Pilot Phase, and will also receive azacitidine. If intolerable side effects are seen, up to 2 more groups will be enrolled and will receive a lower dose of brentuximab vedotin than the group before it. If intolerable side effects are not seen, the next phase of the study will begin.

If you are enrolled in Phase 2, you will receive brentuximab vedotin at the highest dose that was tolerated in Phase 1.

All participants in Phases 1 and 2 will receive the same dose level of azacytidine.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive brentuximab vedotin by vein over 30 minutes on Days 1, 8, and 15 of each 28-day study cycle. If the disease appears to get better, or after cycle 4, the dose and schedule of brentuximab vedotin may be changed to monthly rather than weekly doses.

If you are in Phase 1 or Phase 2, you will also receive azacytidine by vein or as an injection under the skin on Days 1-7 of each cycle.

You may be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

Study Visits:

On Day 1 of each cycle:

* You will have a physical exam.
* Blood (about 2-3 tablespoons) will be drawn for routine tests.
* You will have an EKG.
* Every 3 Cycles (Cycles 3, 6, 9, and so on), if you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

On Days 8 and 22 of Cycle 1, blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 15 of Cycle 1:

* You will have a physical exam.
* Blood (about 2-3 tablespoons) will be drawn for routine tests.

On Day 28 of Cycle 1, then Day 1 of every 2 cycles after that (Cycles 3, 5, 7, and so on), you will have a bone marrow biopsy and/or aspirate to check the status of the disease. After any point that the disease appears to get better, this will be done every 3-4 cycles, or whenever your doctor thinks it is needed.

Length of Treatment:

You may receive the study drug for up to 12 cycles. You will no longer be able to receive the study drug(s) if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the end-of-study visit.

End-of-Study Visit:

About 28 days after your last dose of study drug, you will have an end-of-study visit:

* You will have a physical exam.
* Blood (about 2-3 tablespoons) will be drawn for routine tests.
* You will have an EKG to check your heart function.
* You may have a bone marrow biopsy and/or aspirate to check the status of the disease.
* If you can become pregnant, blood (about 1 teaspoon) or urine will be collected for a pregnancy test.

If the End-of-Study Visit occurs within 21 days of your last dose, you will be called by a member of the study team about 30-37 days after your last dose of study drug. You will be asked how you are feeling and about any side effects you may be having. This call will last about 5 minutes.

This is an investigational study. Brentuximab vedotin is FDA approved and commercially available for the treatment of certain types of lymphoma after previous treatments have failed. Its use in combination with azacitidine is investigational. Azacytidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML).

The study doctor can explain how the study drug(s) are designed to work.

Up to 61 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: 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). arm 2: 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).
Interventions: intervention 1: Brentuximab Vedotin intervention 2: 5-Azacytidine
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents: