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

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ClinicalTrials.gov Identifier: NCT02992860
Recruitment Status : Terminated (Enrollement was stopped due to a recommendation by the IDMC/FDA for a parallel clinical trial with TALA, where potentielly no efficancy could be determined.)
First Posted : December 14, 2016
Last Update Posted : October 25, 2018
Sponsor:
Information provided by (Responsible Party):
GWT-TUD GmbH

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome (MDS) Acute Myeloid Leukemia (AML) Drug: JNJ-56022473 Procedure: Bone marrow analyses and CBC with differential Other: Flow cytometry analyses Other: Central biobanking Procedure: Histopathology analysis Genetic: Cytogenetic analysis Procedure: Serum chemistry Procedure: Automated CBC Procedure: Pregnancy Test Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Agent JNJ-56022473 in MDS and AML Patients Failing Hypomethylating Agent Based Therapy
Actual Study Start Date : July 2016
Actual Primary Completion Date : October 2018
Actual Study Completion Date : October 2018


Arm Intervention/treatment
Experimental: Treatment Arm
JNJ-56022473 will be given intravenously to all subjects at a dose of 9 mg/kg once every 14 days for an initial treatment period of 3 months (6 infusions). Responders will then receive up to 20 additional infusions whereas for non-responders the initial treatment will be followed by a up to 9 months observation period without further JNJ-56022473 treatment. Thus, the individual study duration for a subject will be approx. 1 year. A follow up visit will be performed after 3 months after last study drug administration for all patients to track pregnancy status according to IB.
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.
Other Name: CSL362

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.




Primary Outcome Measures :
  1. Overall hematological response rate [ Time Frame: 3 months ]
    Overall hematological response rate at 3 months (either CR, PR, marrow-CR, HI, SD)


Secondary Outcome Measures :
  1. Toxicity [ Time Frame: 3 or 12 months ]
    Toxicity as measured by NCI CTCAE 4.03

  2. Overall survival [ Time Frame: 1 year ]
  3. Progression-free-survival [ Time Frame: 1 year ]
  4. Overall hematological response rate at 12 months [ Time Frame: 1 year ]
  5. Quality of life EORTC-QLQ30 [ Time Frame: 9 or 15 months ]
    measured by EORTC-QLQ30

  6. Time to treatment failure [ Time Frame: 3 or 12 months ]
  7. Duration of response (best overall response) [ Time Frame: 3 or 12 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02992860


Locations
France
CHU Nantes
Nantes, France
Hospital Archet 1
Nice, France
Hospital Saint Louis
Paris, France
CHU Toulouse
Toulouse, France
Germany
Klinikum Chemnitz gGmbH, Klinik für innere Medizin III
Chemnitz, Germany
Universitätsklinikum Dresden
Dresden, Germany
Heinrich Heine Universität
Dusseldorf, Germany
Marien Hospital GmbH
Dusseldorf, Germany
Technische Universität München, Klinikum rechts der Isar
Munich, Germany
Universitätsklinikum Ulm
Ulm, Germany
Sponsors and Collaborators
GWT-TUD GmbH
Investigators
Principal Investigator: Uwe Platzbecker, Prof. Universitätsklinikum Dresden
Principal Investigator: Lionel Adés, Dr. Hospital Saint Louis Paris

Responsible Party: GWT-TUD GmbH
ClinicalTrials.gov Identifier: NCT02992860     History of Changes
Other Study ID Numbers: SAMBA-trial
11274 ( Other Identifier: GWT-TUD GmbH )
First Posted: December 14, 2016    Key Record Dates
Last Update Posted: October 25, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by GWT-TUD GmbH:
Myelodysplastic Syndrome (MDS)
Acute Myeloid Leukemia (AML)
hypomethylating agent (HMA) treatment
leukemic stem cell
CD123
immunotherapy

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions