Single Agent JNJ-56022473 in MDS and AML Patients FAILING HYPOMETHYLATING AGENT BASED THERAPY

Summary

The outcome of HMA-refractory patients with MDS or AML is dismal with a median survival of 5 months after failure, representing a significant unmet medical need due to the very limited treatment options. In this context, a specific targeting of the leukemic stem cell (LSC) seems a promising option to selectively combat the leukemic progenitor cells. In fact, CD123 is overexpressed in AML and MDS progenitors making it an attractive target for immunotherapy-based approaches. JNJ-56022473 is a promising compound that has been engineered with regard to this strategy and the current phase II trial has the aim to evaluate the overall hematological response rate at 3 months in HMA refractory/relapsed AML and MDS patients.

Conditions

• Myelodysplastic Syndrome (MDS)
• Acute Myeloid Leukemia (AML)

Interventions

DRUG

JNJ-56022473

JNJ-56022473 will be supplied as a lyophilized product containing 100mg of active pharmaceutical ingredient (50 mg/mL after reconstitution with 2.0 mL sterile water for injection). The JNJ-56022473 dose administered will be dependent upon the subject's weight at baseline. The JNJ-56022473 dose should be adjusted in case the subject's weight changes by \> 10%. JNJ- 56022473 will be administered in 250 mL IV infusion over approximately 180 minutes using an infusion pump.

PROCEDURE

Bone marrow analyses and CBC with differential

Bone marrow analyses and CBC with differential will be performed by a central laboratory. If the marrow cannot be aspirated, a biopsy should be performed.

OTHER

Flow cytometry analyses

Characterization of LSCs and blasts (including CD123 and CD38 expression) will be performed as study-related analyses in the context of this protocol by central flow cytometry using bone marrow samples.

OTHER

Central biobanking

Central biobanking of study samples (bone marrow, peripheral blood as well as a buccal swab) will be carried out in Dresden.

PROCEDURE

Histopathology analysis

A bone marrow biopsy is taken whenever it seems necessary to the investigator.

GENETIC

Cytogenetic analysis

The cytogenetic analysis with banding analysis (optional FISH) have to be performed at local labs. Therefore 2 - 5 ml of bone marrow will be collected and analysed.

PROCEDURE

Serum chemistry

For serum chemistry 15 ml (2 x 7,5 ml) of peripheral blood have to be collected.

PROCEDURE

Automated CBC

For CBC a minimum of 3 ml of peripheral blood have to be collected.

PROCEDURE

Pregnancy Test

Serum or urine pregnancy testing β-HCG with a sensitivity of at least 25 mIU/mL is to be done not more than 3 days prior to initiation of JNJ-56022473 in female patients with childbearing potential. Furthermore, serum or urine pregnancy testing has to be done after end of treatment (EoT) visit.

Sponsors & Collaborators

• GWT-TUD GmbH

  lead OTHER

Principal Investigators

• Uwe Platzbecker, Prof. · Universitätsklinikum Dresden

• Lionel Adés, Dr. · Hospital Saint Louis Paris

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-07-31

Primary Completion

2018-10-31

Completion

2018-10-31

Countries

• France
• Germany

Study Locations