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

• Status: Terminated
• Trial end date: 2018-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GWT-TUD GmbH

Criteria

Inclusion Criteria:

• ≥18 years of age

• Diagnosis of AML or MDS

• At least ≥ 5% BM blasts at the time of screening (done by central morphology)

• At least one cytopenia (ANC < 1800/μL or platelet count < 100,000/μL or hemoglobin < 10 g/dL)

• Failure to achieve complete or partial response or hematological improvement after at least six (azacitidine) or four (decitabine) 4-week treatment cycles administered during the past two years OR

• Relapse after initial complete or partial response or hematological improvement observed after at least six (azacitidine) or four (decitabine) 4-week treatment cycles administered during the past two years OR

• Intolerance to treatment with HMA (hypomethylating agents) defined by drug-related ≥ Grade 3 liver or renal toxicity leading to treatment discontinuation during the past two years

• Failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation

• Off all other treatments for AML/MDS for at least four weeks; Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated

• No medical need for or patient opted not to receive induction chemotherapy

• ECOG performance status of 0-2

• Willing to adhere to the prohibitions and restrictions specified in the protocol

• Signed informed consent

Exclusion Criteria:

• Previous treatment with a CD123 agent or T- or NK cell redirecting therapy

• Patients having received intensive chemotherapy to treat HMA failure

• Diagnosis of acute promyelocytic leukemia (APL)

• WBC > 15 GPT/L

• Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast

• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

• Active infection not adequately responding to appropriate therapy

• Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease

• ALT/AST > 2.5 x upper limit of normal

• Serum creatinine > 2.0 mg/dL

• Patients who are unwilling to follow highly effective contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives, contraceptive injections, intrauterine device, , contraceptive patch, surgical sterilization or true sexual abstinence) before entry, at least at screening, throughout the study and within 3 months after last study drug administration

• Female patients with reproductive potential who do not have a negative urine β-HCG pregnancy test at screening and prior to the first study drug administration at visit 1 (day 0) of JNJ-56022473 treatment period.

• Female patients who are lactating