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

NCT04109482 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MB102-CD123-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 4

Brief Summary

A phase 1/2 study to assess the safety and efficacy of MB-102 in patients with relapsed or refractory BPDCN

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Keywords

CD123 CAR-T; BPDCN; Blastic plasmacytoid dendritic cell neoplasm

Outcome Measures

Primary Outcomes (3)

• Phase 1: Safety and Tolerability as measured by the number of patients with treatment related adverse events

  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 in Phase 1

  28 Days

• Phase 1: Maximum Tolerated Dose (MTD) and recommended Phase 2 dose

  To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose of MB-102

  28 Days

• Phase 2: Response Rate of patients with BPDCN

  Relapsed or refractory Blastic Plasmacytoid Dendritic Cell Neoplasm is measured by a response rate which consists of Complete Response and clinical Complete Response and Complete Response with incomplete hematologic recovery (CR + CRc + CRi) at day 28 post infusion

  up to 3 years

Secondary Outcomes (8)

• Phase 2: BPDCN - DOR

  up to 3 years

• Phase 2: BPDCN - PFS

  up to 3 years

• Phase 2: BPDCN - OS

  up to 3 years

• Phase 2: BPDCN - MRD

  up to 3 years

• Phase 2 - Adverse events

  up to 3 years

Study Arms (1)

Relapsed or Refractory BPDCN

EXPERIMENTAL

Treatment with MB-102.

Biological: MB-102; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

MB-102 BIOLOGICAL

The study drug, MB-102 consists of adoptively transferred T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a CD123-specific, CD28-costimulatory chimeric antigen receptor (CAR) as well as a truncated human epidermal growth factor receptor (EGFRt) (CD123.CD28.CD3ζ.EGFRt+T cells) derived from autologous leukapheresis which is administered after a lymphodepletion regimen. Single dose of MB-102 up to 600 x 10 6 CART-T+ cells (Day 0) as defined by Phase 1 will be administered.

Also known as: CD123 CAR-T

Relapsed or Refractory BPDCN

Fludarabine DRUG

Fludarabine 30 mg/m2/day IV (3 days) on days -5, -4, and -3 * A 20% dose reduction (24 mg/m2/day IV (3 days) on days -5, -4, and -3) is required for patients with moderately impaired renal function (creatine clearance ≤ 70 mL/min).

Also known as: Fludara

Relapsed or Refractory BPDCN

Cyclophosphamide DRUG

Cyclophosphamide 300 - 500 mg/m2/day IV (3 days) on days -5, -4, and -3

Also known as: Cytoxan

Relapsed or Refractory BPDCN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Blastic Plasmacytoid Dendritic Cell Neoplasm
• 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.
• Male and female patients ≥ 18 years of age at the time of consent.
• Written informed consent in accordance with federal, local, and institutional guidelines.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.
• Serum albumin ≥ 3.2 g/dL
• 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).
• Females participants of childbearing potential must have a negative serum test.

You may not qualify if:

• 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.
• Contraindication or hypersensitivity to fludarabine or cyclophosphamide.
• Hypersensitivity or known history of allergic reactions attributed to tocilizumab, Cetuximab, or other anti-EGFR -monoclonal antibodies.
• Immunotherapy treatments within 28 days prior to leukapheresis.
• Previous treatment with anti-CD123 CAR-T treatment.
• Previous treatment with non-CAR-T anti-CD123 agents is allowed e.g. tagraxofusp-erzs.
• Previous treatment with any other antileukemic or investigational agent within 7 days of leukapheresis.
• Hydroxyurea is allowed up to 3 days prior to leukapheresis.
• Patients with history or active seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease with CNS involvement.
• 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).
• Patients with active Graft versus Host Disease (GVHD).
• Acute active infection
• Patients being administered prophylactic antibiotics, antivirals, or antifungals are permitted.
• Patients who have any form of primary immunodeficiency, such as severe combined immunodeficiency disease, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS).
• Active infection with hepatitis B or C.

Sponsors & Collaborators

• Mustang Bio: lead

Study Sites (4)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

relmapirazin; fludarabine; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Leukemia; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Lihua E Budde, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: September 30, 2019
• Study Start: February 17, 2020
• Primary Completion: May 17, 2023
• Study Completion: May 17, 2023
• Last Updated: July 22, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)