Refractory Hairy Cell Leukemia Clinical Trial
Official title:
A Phase 1 Trial to Evaluate the Safety of Single Agent Flotetuzumab in Advanced CD123-Positive Hematological Malignancies
Verified date | December 2023 |
Source | City of Hope Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 13 |
Est. completion date | May 5, 2026 |
Est. primary completion date | May 5, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years and older |
Eligibility | Inclusion Criteria: - 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 - Advanced acute leukemia patients with ambiguous lineage or biphenotypic leukemia that failed 2 lines of prior regimens - Patients with any other advanced CD123+ hematological malignancy who have failed standard therapy per the treating physician's judgement - Relapsed or refractory disease as defined above - Tumor expressing CD123 either by flow cytometry or immunohistochemistry staining - Measurable disease of at least 1.5 cm on computed tomography (CT)/magnetic resonance imaging (MRI) for cases without bone marrow involvement - Peripheral blast count < 20,000/ul at the time of initiation of infusion on Cycle 1 Day 1 - Life expectancy of at least 4 weeks - Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy - Absolute neutrophil count (ANC) >= 1000/ul (without bone marrow involvement, performed within 14 days prior to day 1 of protocol therapy) - Platelets >= 75,000/ul (without bone marrow involvement, performed within 14 days prior to day 1 of protocol therapy) - Lumbar puncture to assess presence of central nervous system (CNS) disease if there are symptoms and signs concerning for CNS involvement (performed within 14 days prior to day 1 of protocol therapy) - Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 14 days prior to day 1 of protocol therapy) - Aspartate aminotransferase (AST) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy) - Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 14 days prior to day 1 of protocol therapy) - Left ventricular ejection fraction (LVEF) >= 50%. Note: To be performed within 28 days prior to day 1 of protocol therapy - Corrected QT (QTc) =< 480 ms. Note: To be performed within 28 days prior to day 1 of protocol therapy - If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and DLCO (diffusion capacity) >= 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 90% on room air. Note To be performed within 28 days prior to day 1 of protocol therapy - Calculated or measured creatinine clearance of > 50 ml/min (performed within 14 days prior to Day 1 of protocol therapy) - Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (performed within 14 days prior to day 1 of protocol therapy) - Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy - Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) Exclusion Criteria: - 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 - Clinically significant uncontrolled illness - Females only: Pregnant or breastfeeding - Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures - Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics) |
Country | Name | City | State |
---|---|---|---|
United States | City of Hope Medical Center | Duarte | California |
Lead Sponsor | Collaborator |
---|---|
City of Hope Medical Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Best response of complete remission attained | Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed complete remission [CR]/ complete remission with incomplete count recovery [CRi]/ complete remission with partial hematological recovery [CRh] [Cohort A] or CR/molecular response [MR] [Cohort B]). Remission rates will also be explored based on number/type of prior therapy(ies), the presence of extramedullary disease at the time of starting therapy, disease burden, and CD123 expression intensity. | by the end of induction/re-induction cycles (each cycle is 28 days, up to 6 cycles) | |
Secondary | Minimal residual disease | Assessed by multi-color flow cytometry in ALL the cohorts. | Up to 1 year | |
Secondary | Duration of remission | Will be estimated using the product-limit method of Kaplan and Meier. | Up to 1 year | |
Secondary | Number/percent who bridge to allogeneic hematopoietic cell transplantation (HCT) | Number/percent of patients who proceed to hematopoietic cell transplantation after achieving complete response/ complete remission | Up to 1 year | |
Secondary | Overall survival | Will be estimated using the product-limit method of Kaplan and Meier. | Up to 1 year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT02109224 -
Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection
|
Phase 1 | |
Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
Terminated |
NCT00387426 -
Sunitinib in Treating Patients With Idiopathic Myelofibrosis
|
Phase 2 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Completed |
NCT00003196 -
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
|
N/A | |
Terminated |
NCT01678443 -
Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
|
Phase 1 | |
Active, not recruiting |
NCT01815749 -
Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma
|
Phase 1 | |
Completed |
NCT01588015 -
Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
|
Phase 1 | |
Active, not recruiting |
NCT04578600 -
CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma
|
Phase 1 | |
Withdrawn |
NCT02281279 -
Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma
|
Phase 1/Phase 2 | |
Terminated |
NCT01408043 -
Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma
|
N/A | |
Completed |
NCT00608361 -
Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery
|
Phase 1 | |
Completed |
NCT01254578 -
Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers
|
Phase 1 | |
Completed |
NCT01748721 -
MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma
|
Phase 1 | |
Terminated |
NCT00101205 -
Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma
|
Phase 1 | |
Completed |
NCT00040846 -
Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00005799 -
Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer
|
N/A | |
Withdrawn |
NCT01558778 -
Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant
|
N/A | |
Terminated |
NCT01419795 -
Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant
|
Phase 2 | |
Completed |
NCT00458731 -
Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma
|
Phase 1 |