Bortezomib and Vorinostat in Younger Patients With Refractory or Relapsed MLL Rearranged Hematologic Malignancies

Summary

This study will test the safety and effectiveness of adding bortezomib and vorinostat to other chemotherapy drugs commonly used to treat relapsed or refractory leukemia. Both drugs have been approved by the Food and Drug Administration (FDA) to treat other cancers in adults, but they have not yet been approved tor treatment younger patients with leukemia.

PRIMARY OBJECTIVE

* To estimate the overall response rate of patients with MLL rearranged (MLLr) hematologic malignancies receiving bortezomib and vorinostat in combination with a chemotherapy backbone.

SECONDARY OBJECTIVES

* Estimate event-free and overall-survival.
* Describe toxicities experienced by participants during treatment.

OTHER PRESPECIFIED OBJECTIVES

* To identify all genomic lesions by comprehensive whole genome, exome and transcriptome sequencing on all patients.
* To compare minimal residual disease (MRD) results by three modalities: flow cytometry, polymerase chain reaction (PCR) and deep sequencing.

Conditions

• Mixed Lineage Acute Leukemia
• Acute Myeloid Leukemia
• Acute Lymphoid Leukemia

Interventions

DRUG

Bortezomib

Bortezomib will be given as a 1 mg/mL solution intravenous (IV) push over 3 to 5 seconds. For subcutaneous (SQ) administration, bortezomib will be mixed at 2.5 mg/ml.

DRUG

Vorinostat

Vorinostat should be taken orally (PO) with food.

DRUG

Mitoxantrone

Given by intravenous (IV) injection.

DRUG

Cytarabine

Given by intravenous (IV) injection.

DRUG

Methotrexate

Methotrexate will be given intrathecally (IT) along with hydrocortisone and cytarabine.

DRUG

Hydrocortisone

Hydrocortisone will be given intrathecally (IT) along with methotrexate and cytarabine.

DRUG

Peg-L-Asparaginase

Given by intravenous (IV) or intramuscular (IM) injection.

DRUG

Erwinia L-Asparaginase

To be used in case of allergy or intolerance to PEG-Asparaginase. Given by intravenous (IV) or intramuscular (IM) injection.

DRUG

Dexamethasone

Given orally (PO) or intravenously (IV).

DRUG

Mercaptopurine

Given orally (PO).

DRUG

Doxorubicin

Given intravenously (IV).

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Tanja A. Gruber, MD, PhD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-04-14

Primary Completion

2016-12-31

Completion

2016-12-31

Countries

• United States

Study Locations