Clinical Trials /

Trial to Evaluate the Safety and Efficacy of MB-102 in Patients With BPDCN, AML, and hrMDS.

NCT04109482

Description:

A phase 1/2 study to assess the safety and efficacy of MB-102 in patients with relapsed or refractory BPDCN, AML or high-risk MDS.

Related Conditions:
  • Acute Myeloid Leukemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Myelodysplastic Syndromes
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial to Evaluate the Safety and Efficacy of MB-102 in Patients With BPDCN, AML, and hrMDS.
  • Official Title: A Phase 1/2, Open Label, Multicenter Trial to Assess the Safety and Efficacy of MB-102 in Patients With Relapsed or Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm, Acute Myeloid Leukemia, and High Risk Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: MB102-CD123-001
  • NCT ID: NCT04109482

Conditions

  • Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
  • Acute Myeloid Leukemia
  • Relapsed or Refractory HRMDS

Interventions

DrugSynonymsArms
MB-102CD123 CAR-TRelapsed or Refractory BPDCN
DecitabineDacogenRelapsed or Refractory BPDCN
FludarabineFludaraRelapsed or Refractory BPDCN
CyclophosphamideCytoxanRelapsed or Refractory BPDCN

Purpose

A phase 1/2 study to assess the safety and efficacy of MB-102 in patients with relapsed or refractory BPDCN, AML or high-risk MDS.

Detailed Description

      The Phase 1 portion of the study will determine the maximum tolerated dose of MB-102.

      The Phase 2 portion of the trial is divided into three arms to evaluate the efficacy of
      MB-102 in relapsed or refractory BPDCN (Arm 1), relapsed or refractory AML (Arm 2) and
      demethylation resistant high-risk MDS (Arm 3).
    

Trial Arms

NameTypeDescriptionInterventions
Relapsed or Refractory BPDCNExperimentalTreatment with MB-102.
  • MB-102
  • Decitabine
  • Fludarabine
  • Cyclophosphamide
Relapsed or Refractory AMLExperimentalTreatment with MB-102.
  • MB-102
  • Decitabine
  • Fludarabine
  • Cyclophosphamide
Demethylation resistant high risk MDSExperimentalTreatment with MB-102.
  • MB-102
  • Decitabine
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

        Blastic Plasmacytoid Dendritic Cell Neoplasm

          1. Patients with a diagnosis of BPDCN according to WHO classification (Arber et al.,
             2016) confirmed by hematopathology and histological/cytological evidence of BPDCN in
             the peripheral blood, bone marrow, spleen, lymph nodes, skin and/or other sites who
             have failed one prior therapy.

             Acute Myeloid Leukemia

          2. Must have pathologically confirmed diagnosis of relapsed or refractory AML with early
             relapse (less than 6 months after initial therapy).

             High Risk Myelodysplastic Syndrome

          3. Patients with a diagnosis of high or very high-risk MDS (herein called hrMDS)
             according to IPSS-R classification (Greenberg et al., 2012) who are resistant or
             refractory to at least one course of therapy including demethylating agents
             (decitabine or 5-azacitidine).

             General Inclusion Criteria

          4. Male and female patients ≥ 18 years of age at the time of consent.

          5. Written informed consent in accordance with federal, local, and institutional
             guidelines.

          6. Must be able to adhere to the study visit schedule and other protocol requirements.

          7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          8. Meet the following laboratory criteria:

               -  Absolute lymphocyte count (ALC) > 100/mm3

               -  ALT/SGPT and AST/SGOT < 2.5x the upper limit of normal (ULN) unless due to
                  underlying disease state

               -  Calculated creatinine clearance ≥ 45.0 mL/min as estimated by Cockcroft Gault and
                  dialysis independent

               -  Total bilirubin ≤ 3.0 mg/dL

                    -  Patients with Gilbert's Syndrome must have a total bilirubin < 5.0 mg/dL.

          9. Cardiac ejection fraction ≥ 45%, with no evidence of pericardial effusion as
             determined by an echocardiogram (ECHO) or if not available, a multigated acquisition
             scan (MUGA).

         10. Females participants of childbearing potential must have a negative serum test.

         11. Patients must agree to use a highly effective method of contraception if procreative
             potential exists from the start of the study until one year after the completion of
             lymphodepletion for females and 4 months after completion of lymphodepletion for
             males.

         12. Patients with a previously treated malignancy if treatment of that malignancy was
             completed greater than 2 years before screening and the patient has no evidence of
             disease at the time of screening.

         13. Patients who have previously undergone allogenic or autologous bone marrow transplants
             are allowed.

         14. Confirmed CD-123 positivity on the bone marrow.

        Exclusion Criteria:

          1. Patients with a corticosteroid dependence on doses greater than physiological
             replacement i.e., prednisone no more than 7.5 mg/day or hydrocortisone less than
             12mg/m2/day.

          2. Contraindication or hypersensitivity to decitabine, fludarabine, cyclophosphamide.

          3. Hypersensitivity or known history of allergic reactions attributed to Cetuximab or
             other anti-EGFR -monoclonal antibodies.

          4. Immunotherapy treatments within 28 days prior to screening.

          5. Previous treatment with anti-CD123 CAR-T treatment.

               -  Previous treatment with non-CAR-T anti-CD123 agents is allowed e.g. SL-401.

          6. Previous treatment with any other antileukemic or investigational agent within 14 days
             of leukapheresis.

               -  Hydroxyurea is allowed up to 3 days prior to leukapheresis.

          7. Patients with history or active seizure disorder, cerebrovascular ischemia/hemorrhage,
             dementia, cerebellar disease or any autoimmune disease with CNS involvement.

          8. Patients with known CNS leukemic involvement that are refractory to intrathecal
             chemotherapy and/or cranio-spinal radiation that have NOT been effectively treated to
             complete remission (defined as < 5 WBC/mm3 and no blasts in CSF).

          9. Patients with active Graft versus Host Disease (GVHD).

         10. Acute active infection requiring systemic treatment within 14 days prior to
             leukapheresis.

               -  Patients being administered prophylactic antibiotics, antivirals, or antifungals
                  are permitted.

         11. Patients who have any form of primary immunodeficiency, such as severe combined
             immunodeficiency disease, human immunodeficiency virus (HIV), or acquired immune
             deficiency syndrome (AIDS).

         12. History or active infection with hepatitis B or C.

         13. Patients requiring supplemental oxygen or mechanical ventilation or oxygen saturation
             < 92% on room air.

               -  Patients with an oxygen saturation < 92%, a pulmonary function test with a result
                  of Diffusing capacity of the lungs for carbon monoxide (DLCO) and a forced
                  expiratory volume in one second (FEV1) > 45% predicted will be accepted.

         14. Patients with hepatic cirrhosis.

         15. Pregnant or lactating females.

         16. Any other clinically significant medical disease or condition that, in the
             investigator's opinion, may interfere with protocol adherence or a patient's ability
             to give informed consent.

         17. Patients diagnosed with Acute Promyelocytic Leukemia

               -  Patients who are relapsed or refractory and have previously been treated with
                  anthracycline and/or arsenic trioxide may be allowed to enter the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability as measured by the number of patients with treatment related adverse events
Time Frame:28 Days
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 in Phase 1

Secondary Outcome Measures

Measure:BPDCN - DOR
Time Frame:up to 3 years
Safety Issue:
Description:Duration of Response
Measure:BPDCN - PFS
Time Frame:up to 3 years
Safety Issue:
Description:Progression-Free Survival
Measure:BPDCN - OS
Time Frame:up to 3 years
Safety Issue:
Description:overall survival
Measure:BPDCN - MRD
Time Frame:up to 3 years
Safety Issue:
Description:CR MRD- Response Rate for patients with CR and CRi
Measure:AML - DOR
Time Frame:up to 3 years
Safety Issue:
Description:Duration of Response
Measure:AML - EFS
Time Frame:up to 3 years
Safety Issue:
Description:Event-Free Survival
Measure:AML - RFS
Time Frame:up to 3 years
Safety Issue:
Description:Relapse-Free Survival
Measure:AML - OS
Time Frame:up to 3 years
Safety Issue:
Description:Overall Survival
Measure:AML - MRD
Time Frame:up to 3 years
Safety Issue:
Description:CR MRD- Response Rate for patients with CR and CRi
Measure:high risk MDS - Rate of patients with Hematologic Improvement
Time Frame:up to 3 years
Safety Issue:
Description:Rate of patients achieving Hematologic Improvement in either erythroid, neutrophil or platelet responses.
Measure:high risk MDS - Clinical Benefit Rate
Time Frame:up to 3 years
Safety Issue:
Description:Clinical benefit rate (CR + PR + HI+ marrow CR)
Measure:high risk MDS - Rate of cytogenetic CR
Time Frame:up to 3 years
Safety Issue:
Description:Rate of cytogenetic CR
Measure:high risk MDS - DOR
Time Frame:up to 3 years
Safety Issue:
Description:Duration of Response
Measure:high risk MDS - TI
Time Frame:up to 3 years
Safety Issue:
Description:Transfusion independence
Measure:high risk MDS - Rate of Leukemic Trasformation
Time Frame:up to 3 years
Safety Issue:
Description:Rate of leukemic transformation
Measure:high risk MDS - EFS
Time Frame:up to 3 years
Safety Issue:
Description:Event-Free Survival
Measure:high risk MDS - RFS
Time Frame:up to 3 years
Safety Issue:
Description:Relapse-Free Survival
Measure:high risk MDS - OS
Time Frame:up to 3 years
Safety Issue:
Description:overall survival
Measure:high risk MDS - PFS
Time Frame:up to 3 years
Safety Issue:
Description:Progression-Free Survival
Measure:high risk MDS - MRD
Time Frame:up to 3 years
Safety Issue:
Description:CR MRD- Response Rate for patients with CR or mCR
Measure:Phase 2 - Adverse events
Time Frame:up to 3 years
Safety Issue:
Description:Incidence of treatment-emergent AEs (TEAEs), including SAEs, therapy-related AEs or death.
Measure:Phase 2 -Change from Baseline in the European Organization for Research and Treatment (EORTC) QLQ-C 30 Version 3.0.
Time Frame:up to 3 years
Safety Issue:
Description:The European Organization for Research and Treatment (EORTC) QLQ-C 30 Version 3.0 is an integrated, modular approach for evaluating the quality of life of patients participating in international clinical trials. The questionnaire is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of 5 multi-item scales (physical, role, social, emotional and cognitive functioning) and 9 single items (pain, fatigue, financial impact, appetite loss, nausea/vomiting, diarrhea, constipation, sleep disturbance and quality of life). It utilizes a four-point scales for the first 28 questions which are coded with response categories as "Not at all", "A little", "Quite a bit" and "Very much.". the final two question consist of an overall physical condition questions which have employed a 7-point response scale where the higher number indicates a better overall health.
Measure:Phase 2 - Change from Baseline in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Version 4.0.
Time Frame:up to 3 years
Safety Issue:
Description:The Functional Assessment of Cancer treatment for cancer, and a transplant-specific module, bone marrow transplant (BMT) concerns, that addresses disease and treatment-related questions specific to BMT. It utilizes a 5 point scale assessing physical, social, emotional, functional and other well-being concerns. Response categories are coded as "Not at all", "A little bit", "Somewhat", "Quite a bit" and "Very much.".
Measure:Phase 2 - Change from Baseline in the The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Version 4.0
Time Frame:up to 3 years
Safety Issue:
Description:The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) Version 4.0 is a modular approach to assess patient HQL and leukemia-specific symptoms using a core set of questions as well as a cancer site-specific leukemia subscale. It utilizes a 5 point scale assessing physical, social, emotional, functional and other well-being concerns. Response categories are coded as "Not at all", "A little bit", "Somewhat", "Quite a bit" and "Very much.".
Measure:Phase 2 - Number of patients showing evidence of replication competent lentivirus
Time Frame:up to 1 year
Safety Issue:
Description:To confirm the absence of replication competent lentivirus

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mustang Bio

Trial Keywords

  • CD123 CAR-T
  • AML
  • BPDCN
  • high risk MDS
  • blastic plasmacytoid dendridic cell neoplasm

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