Blincyto Amgen Acrotech BioPharma PH2 Blincyto Marqibo R/R Philadelphi CD19+ ALL

Study Overview
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Brief Summary
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Hypotheses: The Investigator hypothesizes that targeting ALL cells with 2 different modalities, ie liposomal vincristine sulfate as a microtubule inhibitor and blinatumomab as a BITE immuno-oncology therapy, will have at least additive benefits and allow an effective, safe therapeutic option for patients. Further, the Investigator hypothesizes that the combination will result in a high rate of response and thus allow enhanced immunologic recovery. Primary Objectives To evaluate whether the combination will result in a median progression-free survival (PFS) of at least 1 year. To evaluate if the complete remission/complete remission with incomplete hematological recovery (CR/CRi*) rate is ≧ 75% following 2 cycles in adult subjects with R/R Ph- ALL and duration of remission Secondary Objectives To evaluate the rate of Minimal Residual Disease (MRD) and duration To evaluate the proportion of patients who are able to progress to allogeneic transplantation To evaluate the safety of blinatumomab and liposomal vincristine sulfate in combination To evaluate the effect of the combination and response on measures of immune reconstitution

Official Title
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A Phase 2 Single Arm, Multicenter Trial to Evaluate the Efficacy of the BiTE® Antibody Blinatumomab (Blincyto) and Vincristine Sulfate Liposomal Injection (Marqibo) in Adult Subjects With Relapsed/Refractory Philadelphia Negative CD19+ Acute Lymphoblastic Leukemia

Conditions
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B-cell Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Blinatumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Ph-, CD19+ ALL, with any of the following: Relapsed or refractory to at least 2 prior regimens ≥ 5% blasts in the bone marrow or peripheral blood or persistent extranodal/marrow site (such as skin). Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Age ≥ 18 years of age, at the time of informed consent. Subject has provided informed consent. Those unable to provide consent for themselves will not be eligible. Pts may have been exposed to either agent in the past if they had at least 6 months of response from start of therapy AND it has been at least 6 months since their last dose of either agent. Exclusion Criteria: History of malignancy other than ALL within 3 years prior to start of protocol-required therapy with the exception of: Malignancy treated with curative intent and with no known active disease present for 2 years before enrollment and felt to be at low risk for recurrence by the treating physician Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated cervical carcinoma in situ without evidence of disease Adequately treated breast ductal carcinoma in situ without evidence of disease Prostatic cancer without evidence of progression for 1 year. History or presence of clinically relevant CNS pathology as adult seizures, recent stroke (within 1 year), severe brain injuries, Parkinson's disease, psychosis With the exception of CNS leukemia that is well controlled with therapy prior to enrolling on this study. A negative CNS evaluation for active disease is required within 3 months of enrollment in those with prior history within one year of active CNS disease . Current severe autoimmune disease or history of autoimmune disease with potential CNS involvement such as lupus, sjogren's, psoriasis, multiple sclerosis, wegener's granulomatosis. Allogeneic HSCT within 12 weeks prior to start of blinatumomab/marqibo Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment of more than 10 mg prednisone daily (or equivalent) Cancer chemotherapy or immunotherapy within 2 weeks prior to start of blinatumomab/marqibo. Administration of dexamethasone and hydrea permitted within the 21 day screening period. Subject received prior anti-CD19 therapy ARE eligible however if they received prior blinatumomab, however they are ineligible if they did not have a response to it lasting at least 6 months; also they are ineligible if they had exposure to blinatumomab within 6 months of starting therapy on this study. Abnormal screening laboratory values as defined below: AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase ≥ 5 x upper limit of normal (ULN) Total bilirubin ≥ 3 x ULN (unless related to Gilbert´s or Meulengracht disease) Creatinine ≥ 3 ULN or creatinine clearance < 40 mL/min (calculated) Known infection with human immunodeficiency virus (HIV) or chronic active infection with hepatitis B virus (PCR positive) or hepatitis C virus (PCR positive). Subject is pregnant or breast feeding Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving blinatumomab/marqibo and for an additional 3 months after the last dose of protocol-specified therapy Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception for at least an additional 3 months after the last dose of protocol-specified therapy Male who has a pregnant partner, and is not willing to use a condom during sexual activity for 3 months after the last dose of protocol-specified therapy Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study(s). The 30 days is calculated from day 1 of blinatumomab treatment. Subject has known severe sensitivity to immunoglobulins or any of the products or components to be administered during dosing. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>A single cycle of blinatumomab which includes 4 weeks of CIVI of blinatumomab followed by a 2 week treatment free interval | Drug: Blinatumomab<br>* liposomal vincristine 2.25 mg/m2 weekly x 3 per cycle (weeks 3-5 in cycle 1 and 2-4 in subsequent cycles)<br>* Other names: liposomal vincristine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | patient report | At 1 year | 
| Complete remission/complete remission with incomplete hematological recovery (CR/CRi*) rate | lab reports | End of Cycle 2 (1 cycle is 6 weeks in duration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal Residual Disease (MRD) and duration | Flow Measurement | End of Cycle 2 (1 cycle is 6 weeks in duration) | 
| Minimal Residual Disease (MRD) and duration | Flow Measurement | End of Therapy (up to 58 weeks) | 
| Proportion of patients able to progress to allogeneic transplantation | Investigator reported | End of study (up to 58 weeks) | 
| Safety of blinatumomab and liposomal vincristine sulfate in combination, as measured by rate of toxicity | Investigator report of toxicities | Through all cycles of therapy (up to 58 weeks) | 
| Immune reconstitution, as measured by the immune reconstitution panel | immune reconstitution panel | End of study (up to 58 weeks) |