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

NCT ID: NCT04109482

Last Updated: 2024-07-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-17
• Study Completion Date: 2023-05-17

Brief Summary

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

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 will evaluate the efficacy of MB-102 in relapsed or refractory BPDCN.

Conditions

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Relapsed or Refractory BPDCN

Treatment with MB-102.

Group Type: EXPERIMENTAL

MB-102

Intervention Type: 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.

Fludarabine

Intervention Type: 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).

Cyclophosphamide

Intervention Type: DRUG

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

Interventions

MB-102

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.

Intervention Type: BIOLOGICAL

Fludarabine

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).

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Other Intervention Names

CD123 CAR-T; Fludara; Cytoxan

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.

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

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

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

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

6. 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

7. 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).

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

9. 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.

10. 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.

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

12. Centrally confirmed CD-123 positivity on the bone marrow, or for patients without bone marrow involvement local pathology assessments within 28 days from Screening, showing evidence of CD-123 positivity of skin/lymph node biopsy.

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 fludarabine or cyclophosphamide.

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

4. Immunotherapy treatments within 28 days prior to leukapheresis.

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

• Previous treatment with non-CAR-T anti-CD123 agents is allowed e.g. tagraxofusp-erzs.

6. Previous treatment with any other antileukemic or investigational agent within 7 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

• 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. 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) of ≥ 40% of predicted and a forced expiratory volume in one second (FEV1) > 45% predicted will be accepted.

14. Patients with decompensated hepatic cirrhosis/liver failure.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mustang Bio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lihua E Budde, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Duke University

Durham, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

MB102-CD123-001

Identifier Type: -

Identifier Source: org_study_id