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.
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.
Recruiting
Phase 1/Phase 2
Drug | Synonyms | Arms |
---|---|---|
MB-102 | CD123 CAR-T | Relapsed or Refractory BPDCN |
Decitabine | Dacogen | Relapsed or Refractory BPDCN |
Fludarabine | Fludara | Relapsed or Refractory BPDCN |
Cyclophosphamide | Cytoxan | Relapsed or Refractory BPDCN |
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).
Name | Type | Description | Interventions |
---|---|---|---|
Relapsed or Refractory BPDCN | Experimental | Treatment with MB-102. |
|
Relapsed or Refractory AML | Experimental | Treatment with MB-102. |
|
Demethylation resistant high risk MDS | Experimental | Treatment with MB-102. |
|
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 |
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 |
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 |
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Mustang Bio |