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

NCT04448834 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: Pro00104913
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

B-cell Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Minimal Residual Disease (MRD) and duration

  End of Cycle 2 (1 cycle is 6 weeks in duration)

• Minimal Residual Disease (MRD) and duration

  End of Therapy (up to 58 weeks)

• Proportion of patients able to progress to allogeneic transplantation

  End of study (up to 58 weeks)

• Safety of blinatumomab and liposomal vincristine sulfate in combination, as measured by rate of toxicity

  Through all cycles of therapy (up to 58 weeks)

• Immune reconstitution, as measured by the immune reconstitution panel

  End of study (up to 58 weeks)

Study Arms (1)

Treatment

EXPERIMENTAL

A single cycle of blinatumomab which includes 4 weeks of CIVI of blinatumomab followed by a 2 week treatment free interval

Drug: Blinatumomab

Interventions

Blinatumomab DRUG

liposomal vincristine 2.25 mg/m2 weekly x 3 per cycle (weeks 3-5 in cycle 1 and 2-4 in subsequent cycles)

Also known as: liposomal vincristine

Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Dorothy Sipkins, MD, PhD: lead
• Amgen: collaborator
• Acrotech Biopharma Inc.: collaborator

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Novant Health Cancer Institute and Innovation Center

Winston-Salem, North Carolina, 27101, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

blinatumomab; Vincristine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Dorothy Sipkins, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Instructor in the Department of Medicine

Study Record Dates

• First Submitted: June 22, 2020
• First Posted: June 26, 2020
• Study Start: January 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)