Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02152956
Other study ID # CP-MGD006-01
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date June 9, 2014
Est. completion date July 5, 2022

Study information

Verified date January 2024
Source MacroGenics
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Open-label, multi-dose, single-arm, multi-center, Phase 1/2 study conducted in three segments: the Single Patient Dose Escalation Segment (complete), followed by the Multi-Patient Dose Escalation Segment (complete) and the Maximum Tolerated Dose and Schedule (MTDS) Expansion Cohort Segment (closed). Having characterized safety and determined the maximum tolerated dose and schedule, the primary objective of this study now is to assess the anti-neoplastic activity of flotetuzumab in patients with PIF/ER AML, as determined by the proportion of patients who achieve CR or CRh. Starting with Cycle 2, patients who are benefiting from flotetuzumab may receive up to a maximum of 8 cycles of treatment. Patients will receive daily increasing doses of flotetuzumab for the first week of Cycle 1 (Lead-In Dosing) followed by 3 weeks of continuous intravenous infusion at a the assigned dose. Subsequent cycles are each 4 weeks of continuous infusion at the assigned dose. Dosing may continue for up to 8 cycles. Follow up visits may continue for 6 months after treatment is discontinued.


Recruitment information / eligibility

Status Terminated
Enrollment 244
Est. completion date July 5, 2022
Est. primary completion date July 5, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL)] according to World Health Organization (WHO) classification - Patients with AML must meet one of the following criteria, a or b: 1. Primary Induction Failure (PIF) AML, defined as disease refractory to either, i or ii: - i. An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. Examples include but are not limited to: 1 cycle of high dose cytarabine (HiDAC) containing regimen, 1 cycle of liposomal cytarabine and daunorubicin, 2 cycles of standard dose cytarabine containing regimen - ii. For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens: i = 2 but = 4 cycles of Bcl-2 inhibitors in combination with azacitidine, decitabine, or low dose cytarabine, or ii = 2 but = 4 cycles of gemtuzumab ozogamicin monotherapy 2. Early relapse (ER) AML, defined as AML in first relapse with initial CR1 duration < 6 months - Limit of 3 prior lines of therapy (excluding focal radiation therapy for palliative purposes): up to 2 induction (induction, re-induction) or 1 induction plus/minus 1 consolidation attempt, followed by a maximum of 1 salvage/re-induction attempt. - Eastern Cooperative Oncology Group (ECOG) performance status =2 - Life expectancy of at least 4 weeks - Peripheral blast count </= 20,000/mm3 at the time of first dose - Acceptable laboratory parameters and adequate organ reserve Exclusion Criteria: - History of allogeneic stem cell transplantation - Prior treatment with an anti-CD123-directed agent - Need for concurrent other cytoreductive chemotherapy - Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically and with stable supplementation) - Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed. - Antitumor therapy or investigational agent within 14 days or 5 half-lives of Cycle 1 Day 1. - Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or the equivalent, except steroid inhaler, otic preparations, nasal spray or ophthalmic solution - Use of immunosuppressant medications in the 2 weeks prior to Cycle 1 Day 1 - Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to Cycle 1 Day 1 - Known central nervous system (CNS) leukemia - Active uncontrolled infection (including, but not limited to viral, bacterial, fungal, or mycobacterial infection), - Known human immunodeficiency virus infection, unless all of the following criteria are met: CD4+ count = 350 cells/µL, undetectable viral load, and receiving highly active antiretroviral therapy. - Known, active, history of or current acute or chronic hepatitis B or C virus (HBV) infection (as evidenced by detectable HBV surface antigen and HBV DNA = 500 IU/mL), - History of hepatitis C virus (HCV) infection, unless the infection has been treated and cured, - Active SARS-CoV-2 infection. While SARS-CoV-2 testing is not mandatory for study entry, testing for ongoing infection should follow local clinical practice guidelines/standards. Participants with a positive test result for ongoing SARS-CoV-2 infection, known asymptomatic infection, or suspected infection are excluded unless or until asymptomatic and with subsequent negative SARS-CoV-2 laboratory test.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Flotetuzumab 3 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Flotetuzumab 10 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 30 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 100 ng/kg/day, 4 days on and 3 days off
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 300 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 500 ng/kg/day, 4 days on 3 days off, after one-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART® molecule.
Flotetuzumab 500 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 700 ng/kg/day, 4 days on 3 days off, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Flotetuzumab 700 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.
Drug:
Ruxolitinib
Oral inhibitor of JAK kinase
Biological:
Flotetuzumab 300 ng/kg/day, continuous infusion, after multi-step lead-in dose
Flotetuzumab is a CD123 x CD3 bispecific antibody-based molecular construct referred to as a DART molecule.

Locations

Country Name City State
France Institut Paoli-Calmettes Marseille
France Centre Hospitalier Universitaire de Nantes Nantes
France Institut Universitaire du Cancer de Toulouse-Oncopole Toulouse
France CHRU de Tours - Hôpital Bretonneau Tours
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden Dresden
Germany Universitätsklinik Hamburg-Eppendorf Hamburg
Germany Universitätsklinikum Leipzig Leipzig
Germany Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz
Germany III. Med. Klinik-Klinikum rechts der Isar-Technische Universität München Munich
Germany Medizinische Klinik und II, Universitätsklinikum Würzburg Würzbur
Israel Rambam Health Care Campus Haifa
Israel Shaare Zedek Medical Center Jerusalem
Italy Policlinico Sant'Orsola Malpighi Bologna
Italy Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Meldola
Italy University Vita-Salute San Raffaele Milano
Italy Unità Operativa di Ematologia Ospedale Santa Maria delle Croci Ravenna
Netherlands University Medical Center Groningen Groningen
Netherlands Erasmus University Medical Center Rotterdam
Spain Universitat Autonomaa de Barcelona (UAB) - Hospital de la Santa Creu i de Sant Pau Barcelona
Spain Hospital Universitario 12 de Octubre Madrid
United Kingdom King's Health Partners London
United Kingdom The Christie NHS Foundation Trust Manchester
United States University of Michigan Ann Arbor Michigan
United States Emory University Atlanta Georgia
United States University of Maryland Baltimore Maryland
United States University of North Carolina Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Cleveland Clinic Cleveland Ohio
United States City of Hope National Medical Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States UCSD Moores Cancer Center La Jolla California
United States Loyola University Chicago - Cardinal Bernadin Cancer Center Maywood Illinois
United States Medical College of Wisconsin Milwaukee Wisconsin
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States Providence Portland Medical Center Portland Oregon
United States Washington University School of Medicine Saint Louis Missouri
United States UCSF - Helen Diller Family Comprehensive Cancer Center San Francisco California
United States University of California, San Francisco San Francisco California
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Stony Brook Medicine Stony Brook New York
United States Moffitt Cancer Center Tampa Florida
United States Georgetown University - Lombardi Cancer Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
MacroGenics

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Efficacy Based on CR or CRh Rate Proportion of patients achieving a best response of CR (morphologic CR [mCR], cytogenetic CR [CRc], molecular CR [CRm], or CRh per Interworking Group AML response criteria.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
up to 14 months
Secondary Overall Complete Response Rate Rate of CR + CRh + CRi (CR with incomplete blood cell recovery [CR with incomplete neutrophil {CRn}or platelet recovery {CRp}]) + MLFS (morphologic leukemia-free state) up to 14 months
Secondary CR Rate Proportion of patients achieving a best response of CR (morphologic CR [mCR], cytogenetic CR [CRc], or molecular CR [CRm] per Interworking Group AML response criteria.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
up to 14 months
Secondary CRh Rate Proportion of patients achieving a best response of CRh per Interworking Group AML response criteria.
CRh is defined as: CR with partial hematologic recovery.
up to 14 months
Secondary Overall Response Rate Proportion of patients achieving a best response of CR, CRh, CRi, MLFS or partial response per Interworking Group AML response criteria.
CR is defined as mCR, CRc, CRm or CRh. mCR is defined as: normal. neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and. no extramedullary disease.
CRc is defined as: CR with no evidence of cytogenetic abnormalities in the bone marrow.
CRm is defined as: CR with no evidence of molecular abnormalities in the bone marrow.
CRh is defined as: CR with partial hematologic recovery.
up to 14 months
Secondary HSCT Rate Rate of successful hematopoietic stem cell transplantation (HSCT) after the start flotetuzumab treatment and before subsequent therapy. up to 8 months
Secondary Occurrence of Dose Limiting Toxicity Maximum Tolerated Dose/Schedule: the MTDS is defined as the highest dose/schedule administered during any Cohort in the study at which the incidence of DLT is < 33% during the first cycle of MGD006 treatment. Cycle 1 of a 28 day cycle.
Secondary Occurrence of Adverse Events (AEs) Cycle 1 through end of treatment up to 9 months
Secondary Occurrence of Serious Adverse Events (SAEs) up to 9 months
Secondary Participants With Anti-drug Antibodies Occurrence of anti-drug antibody Study Day 1, then every 28 days through 28-days after the last dose (up to 8 months)
Secondary Number of Patients With Infusion Related Reaction (IRR) Determine safety and efficacy of tocilizumab in the treatment of IRR/CRS as measured by incidence of IRR/CRS During study drug administration (up to 8 months)
Secondary Number of Patients With Cytokine Release Syndrome (CRS) up to 9 months
Secondary Maximum Serum Concentration of Flotetuzumab Measure the pharmacokinetics (PK) of flotetuzumab Study day 1, then every 28 days and 28 days after the last dose (up to 8 months)
Secondary Post-baseline Transfusion Independence Rate The number of patients who were transfusion-dependent at baseline and did not receive transfusions during any consecutive 56-day period will be calculated. The number of patients who are transfusion independent at baseline and remain independent during any 56-day post-baseline period will also be calculated. 56 days
Secondary Number of Patients Alive at 6 Months 6 months
Secondary Event-free Survival Time from the first dose of study drug until date of evidence of primary refractory disease to flotetuzumab, relapse from CR, CRh or CRi, or death from any cause, whichever occurs first. Up to 2 years
Secondary Mortality Rate number of deaths from any cause within 30, 60, 90, or 180 days of first dose of study drug Throughout the study, up to 3 years.
Secondary Number of Patients Alive at 12 Months Number of patients alive at 1 year from first dose of study drug 1 year
Secondary Median Time to Response Time from first dose of study drug to first CR, CRh, CRi, or MLFS up to 14 months
Secondary Duration of Response of Patients With CR or CRh Time of initial documentation of response to the time of disease relapse or death due to any cause, whichever occurs first. Up to 2 years
Secondary Overall Survival Time from first dose to death from any cause Up to 2 years
Secondary Rate of Hospitalization for Patients in the Expansion Cohort After Initial Discharge Initial dosing procedures were performed as a hospital inpatient. Incidence rate of hospitalization after discharge from the hospital will be calculated up to 8 months
Secondary Duration of Hospitalization for Patients in the Expansion Cohort Duration of hospitalization will be characterized after discharge from initial dosing will be characterized up to 8 months
See also
  Status Clinical Trial Phase
Completed NCT03118466 - Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia Phase 2
Not yet recruiting NCT06313437 - Revumenib in Combination With 7+3 + Midostaurin in AML Phase 1
Withdrawn NCT03444649 - Epacadostat, Idarubicin and Cytarabine (EIC) in AML Phase 1
Withdrawn NCT02905994 - Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia Phase 1
Recruiting NCT02261779 - Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible Phase 1/Phase 2
Completed NCT00333190 - CD8+ T Cell Depletion for GVHD Prophylaxis After Peripheral Blood Stem Cell Transplantation N/A
Completed NCT00246649 - Stem Cell Transplant With Specially Treated Cells in Treating Patients With Acute Leukemia N/A
Terminated NCT04079738 - Study Augmenting TAK-659 Action in Relapsed/Refractory AML by Addition Ofthe Proteasome Inhibitor Ixazomib Phase 1/Phase 2
Completed NCT03466320 - DEPLETHINK - LymphoDEPLEtion and THerapeutic Immunotherapy With NKR-2 Phase 1/Phase 2
Withdrawn NCT03138395 - iCare3: Monitoring Circulating Cancer DNA After Chemotherapy in MDS and AML N/A
Terminated NCT01570465 - Prospective Study on Severe Infections on Acute Myeloid Leukemia (AML) Patients
Completed NCT04443751 - A Safety and Efficacy Study of SHR-1702 Monotherapy in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) Phase 1
Terminated NCT03761069 - Study of PTC299 (Emvododstat) in Relapsed/Refractory Acute Leukemias Phase 1
Completed NCT02631993 - Photochemotherapy and Graft-versus-leukemia in Acute-leukemia N/A
Completed NCT02575963 - Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients Phase 1/Phase 2
Completed NCT00863148 - Allogeneic Stem Cell Transplant With Clofarabine, Busulfan and Antithymocyte Globulin (ATG) for Adult Patients With High-risk Acute Myeloid Leukemia/Myelodysplastic Syndromes (AML/MDS) or Acute Lymphoblastic Leukemia (ALL) Phase 2
Completed NCT00780598 - Safety and Anti-Disease Activity of Oral Tosedostat (CHR-2797) in Elderly Subjects With Refractory or Relapsed AML Phase 2
Completed NCT00542971 - Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006) Phase 1/Phase 2
Completed NCT00761449 - Lenalidomide in High-risk MDS and AML With Del(5q) or Monosomy 5 Phase 2
Terminated NCT00176930 - Stem Cell Transplant for Hematological Malignancy N/A