Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies

NCT04681105 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 20472NCI-2020-08118P30CA033572
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Conditions

Recurrent Acute Leukemia; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hairy Cell Leukemia; Recurrent Hematologic Malignancy; Recurrent Hodgkin Lymphoma; Recurrent T Acute Lymphoblastic Leukemia; Refractory Acute Leukemia; Refractory B Acute Lymphoblastic Leukemia; Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Hairy Cell Leukemia; Refractory Hematologic Malignancy; Refractory Hodgkin Lymphoma; Refractory T Acute Lymphoblastic Leukemia; Systemic Mastocytosis

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 except infusion-related reaction (IRR)/cytokine release syndrome (CRS) which will be by the modified criteria proposed by Lee et al. Safety and toxicity will be assessed for each cohort independently. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 30 days post-treatment

Secondary Outcomes (5)

• Best response of complete remission attained

  by the end of induction/re-induction cycles (each cycle is 28 days, up to 6 cycles)

• Minimal residual disease

  Up to 1 year

• Duration of remission

  Up to 1 year

• Number/percent who bridge to allogeneic hematopoietic cell transplantation (HCT)

  Up to 1 year

• Overall survival

  Up to 1 year

Study Arms (1)

Treatment (flotetuzumab)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles. CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

Drug: Acetaminophen; Drug: Dexamethasone; Drug: Diphenhydramine; Biological: Flotetuzumab; Drug: Ibuprofen; Drug: Ranitidine

Interventions

Acetaminophen DRUG

Given PO

Also known as: APAP, Paracetamol, Tylenol

Treatment (flotetuzumab)

Dexamethasone DRUG

Given IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (flotetuzumab)

Flotetuzumab 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, RES234, S80880

Treatment (flotetuzumab)

Ibuprofen DRUG

Given PO

Also known as: (.+ -.)-p-Isobutylhydratropic acid, Advil, Motrin, p-Isobutylhydratropic acid

Treatment (flotetuzumab)

Diphenhydramine DRUG

Given IV or PO

Also known as: FAR 90X2, PM 255, Probedryl, Rigidyl, S51, Syntedril

Treatment (flotetuzumab)

Ranitidine DRUG

Given IV

Treatment (flotetuzumab)

Eligibility Criteria

• Age: 12 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 targeted 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 myelocytic 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, not actively on systemic immunosuppressive therapy and off calcineurin inhibitors for at least 4 weeks prior to start 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 lumbar 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 (left ventricular ejection fraction \< 50%)
• Major trauma or surgery within 4 weeks before enrollment

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

  PMID: 35622074 DERIVED

MeSH Terms

Conditions

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

Interventions

Acetaminophen; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Diphenhydramine; Ibuprofen; Ranitidine

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; Histiocytic Disorders, Malignant; Leukemia; Neoplasms by Site; Skin Neoplasms; Hematologic Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Mast Cell Activation Disorders

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Ethylamines; Benzhydryl Compounds; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ibrahim T Aldoss

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2020
• First Posted: December 23, 2020
• Study Start: November 18, 2020
• Primary Completion: August 5, 2025
• Study Completion: August 5, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)