Flotetuzumab in Treating Patients With Recurrent or Refractory CD123 Positive Blood Cancer

NCT03739606 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 18368NCI-2018-02320
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well flotetuzumab works in treating patients with CD123 positive blood cancer that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as flotetuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Acute Biphenotypic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hairy Cell Leukemia; Interleukin-3 Receptor Subunit Alpha Positive; Recurrent Acute Lymphoblastic Leukemia; Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hematologic Malignancy; Recurrent Hodgkin Lymphoma; Refractory Acute Lymphoblastic Leukemia; Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm; Refractory Hematologic Malignancy; Refractory Hodgkin Lymphoma; Systemic Mastocytosis

Outcome Measures

Primary Outcomes (1)

• Best response of complete remission (complete remission [CR], complete remission with incomplete count recovery [CRi], complete remission with partial hematological recovery [CRh])

  Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed CR/CRi/CRh).

  Within the first 4 courses (112 days)

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 1 year

• Minimal residual disease (MRD) as assessed by multi-color flow cytometry

  Up to 1 year

• Duration of remission

  Up to 1 year

• Number who bridge to allogeneic hematopoietic cell transplantation

  Up to 1 year

• Percent who bridge to allogeneic hematopoietic cell transplantation

  Up to 1 year

Study Arms (1)

Treatment (flotetuzumab)

EXPERIMENTAL

Patients receive flotetuzumab IV continuously for 28 days. Patients who achieve partial response or stable disease or any clinical benefit (PR, SD) that did not meet CR, CRi, CRh or MLFS criteria receive a second 28-day continuous flotetuzumab IV infusion. Patients who achieve CR/CRi/CRh/MLFS after course 1 or course 2 receive flotetuzumab IV at a 4 days on-3 days off schedule. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: Anti-CD123/CD3 Monoclonal Antibody MGD006

Interventions

Anti-CD123/CD3 Monoclonal Antibody MGD006 BIOLOGICAL

Given IV

Also known as: CD123 x CD3 DART Bi-Specific Antibody MGD006, CD123 x CD3 Dual Affinity Re-Targeting Bi-Specific Antibody MGD006, MGD006

Treatment (flotetuzumab)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative.
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Histologically confirmed diagnosis of
• Cohort A. Acute lymphoblastic leukemia
• B-cell phenotype: patients with relapsed or refractory ALL who have received at least 2 prior regimens and failed or are ineligible for CD19-based target therapy
• T-cell phenotype: patients with relapsed or refractory who have received at least 1 prior regimen
• Cohort B. Other CD123+ hematological malignancies that failed standard regimens, excluding acute myeloid leukemia and myelodysplastic syndrome
• Blastic plasmacytoid dendritic cell neoplasm (BPDCN) patients who have failed or relapsed after initial therapy
• Chronic myeloid leukemia (CML) patients who have failed or relapsed or ineligible for third generation tyrosine kinase inhibitor (ponatinib)
• Hairy cell leukemia patients who have failed or progressed shortly after purine analogs or failed 2 cycles of purine analog
• Systemic mastocytosis patients who have failed or progressed on midostaurin
• Hodgkin lymphoma patients who have failed or relapsed after PD-1/PD-L1- inhibitors and brentuximab vedotin

You may not qualify if:

• Autologous or allogeneic hematopoietic cell transplant performed within 100 days prior to study drug administration in day 1 of cycle 1 of protocol therapy. However, patients who received allogeneic hematopoietic cell transplantation (HCT) more than 100 days are allowed if no active graft versus host disease (GVHD) \> grade 1 and not actively on systemic immunosuppressive therapy
• Chemotherapy, radiation therapy, biological therapy, within 14 days prior to day 1 of protocol therapy. Maintenance-type ALL chemotherapies, including vincristine and mercaptopurine are allowed up to 7 days before starting therapy. High dose steroids are allowed up to 3 days before starting therapy. Cytoreduction with hydroxyurea is allowed to control leukocytosis until to the day of starting therapy. Hydroxyurea can be given during cycle 1 of flotetuzumab administration to control leukocytosis but need to be discussed with the study PI
• Previous treatment with immunotherapeutic agents (for example chimeric antigen receptor \[CAR\] T cells, long acting bispecific antibodies, etc) in the 28 days period prior to study drug administration on day 1 cycle 1, with the exception of short-half bispecific antibodies (blinatumomab) where the washout period is only 14 days
• Requirement, at the time of study entry, for concurrent steroid \> 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, nasal spray or ophthalmic solution
• Use of immunosuppressant medications (other than steroid as noted above) in the 2 weeks prior to study drug administration (cycle 1 day 1)
• Known central nervous system involvement. Patients with suspected CNS involvement must be evaluated by lumber puncture and be free of CNS disease prior to study entry. Previously treated CNS involvement is allowed provided adequate treatment has been provided and the patient is free of CNS disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to flotetuzumab
• Any active untreated autoimmune disorders (with the exception of vitiligo)
• Dementia or altered mental status that would preclude sufficient understanding to provide informed consent
• Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed
• Active uncontrolled infection
• Significant pulmonary compromise
• Unstable angina or clinically significant heart disease
• Major trauma or surgery within 4 weeks before enrollment
• Clinically significant uncontrolled illness

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Hairy Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Hematologic Neoplasms; Hodgkin Disease; Mastocytosis, Systemic

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Lymphoma; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Mast Cell Activation Disorders

Study Officials

• Ibrahim Aldoss, MD

  City of Hope Medical Center

  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

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: November 14, 2018
• Study Start: October 20, 2020
• Primary Completion: October 20, 2020
• Study Completion: October 20, 2020
• Last Updated: December 17, 2020

Record last verified: 2020-12