Back to resultsLintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Lintuzumab-Ac-225 (Dose 1: 0.25 μCi/kg Ac-225 with 1.6 μg/kg lintuzumab)
Cladribine
Cytarabine
Mitoxantrone
G-CSF
Lintuzumab-Ac-225 (Dose 2: 0.50 μCi/kg Ac-225 with 3.2 μg/kg lintuzumab)
Lintuzumab-Ac-225 (Dose 3: 0.75 μCi/kg with 4.7μg/kg lintuzumab)
Lintuzumab-Ac-225 (Dose 4: 1.00 μCi/kg with 6.4 μg/kg lintuzumab)
Lintuzumab-Ac-225 (Dose 5: 1.25 μCi/kg with 8.0 μg/kg lintuzumab)
Lintuzumab-Ac-225 (Recommended Phase 2 Dose)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute myeloid leukemia, Relapsed/refractory acute myeloid leukemia, CLAG-M, Lintuzumab
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years at the time of informed consent.
- Morphologically documented primary AML or secondary AML [from prior conditions such as Myelodysplastic Syndrome (MDS), myeloproliferative neoplasm (MPN)] or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
- In first or subsequent relapse or refractory status after prior therapy, with or without prior hematopoietic stem cell transplant (HSCT). Patients with MDS and progression to AML on hypomethylating agents will also be included.
- Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
- Greater than 25% of blasts must be CD33 positive on flow cytometry using Phycoerythrin (PE) labeled anti-CD33 antibody.
Patients must meet the following clinical laboratory criteria:
- Total bilirubin ≤ 2 x the upper limit of the normal range (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
- Calculated creatinine clearance ≥ 50 mL/min
- Resting left ventricular ejection fraction (LVEF) > 40%
- Female patients must agree to avoid becoming pregnant, and male patients should avoid impregnating a female partner.
Exclusion Criteria:
- Acute Promyelocytic Leukemia.
- Active severe infection not well controlled by antibacterial or antiviral therapy.
- Known infection with human immunodeficiency virus.
- Patients with documented pulmonary disease, with a diffusing capacity of the lungs for carbon monoxide (DLCO) and/or forced expiratory volume in one second (FEV1) <65%, or history of dyspnea at rest, or requiring oxygen.
- Pregnant or breast feeding women.
- Prior chemotherapy or radiotherapy within 14 days of study entry unless fully recovered from adverse effects due to treatment, at investigator's discretion.
- Active malignancy within 2 years of entry, except previously treated melanoma grade 2 or less, non-melanoma skin cancer, carcinoma in situ, or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of progressive disease based on prostate-specific antigen (PSA) levels and are not on active therapy. Active malignancy is malignancy receiving treatment.
Sites / Locations
- Froedtert Hospital and the Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Lintuzumab Ac225 (Dose 1 - 0.25 μCi/kg Ac-225 with 1.6 μg/kg lintuzumab)
Lintuzumab Ac225 (Dose 2 - 0.50 μCi/kg Ac-225 with 3.2 μg/kg lintuzumab)
Lintuzumab Ac225 (Dose 3 - 0.75 μCi/kg Ac-225 with 4.7μg/kg lintuzumab)
Lintuzumab Ac225 (Dose 4 - 1.00 μCi/kg Ac-225 with 6.4 μg/kg lintuzumab)
Lintuzumab Ac225 (Dose 5 - 1.25 μCi/kg Ac-225 with 8.0 μg/kg lintuzumab)
Lintuzumab Ac225 Recommended Phase 2 Dose (RP2D)
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
The maximum-tolerated dose for lintuzumab-Ac225 is defined as the highest level at which no more than one patient experiences a dose-limiting toxicity. The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Outcomes
Primary Outcome Measures
The number of subjects with dose-limiting toxicities.
Dose-escalation will be conducted according to a 3+3 design with a five-patient expansion cohort at the recommended phase 2 dose. The initial dose of Lintuzumab-Ac225 will be 0.25 micro-Curie (μCi)/kg (Dose level 1), and the highest dose administered will be 1.25 μCi/kg.
if 0/3 pts have no dose-limiting toxicity (DLT), new patients enter next dose level.
if 1/3 pts has DLT, 3 pts treated at same dose level.
if 0/3 pts at that dose level has DLT, new pts enter higher level.
if 1 or more of the additional 3 pts has a DLT, no further pts started at dose level, preceding dose is the MTD.
if 2/3 of initially dosed patients have a DLT on first dose, study terminated.
if 0/3 have DLT at highest dose, additional 3 enrolled.
Maximum-tolerated dose.
Defined as the dosage with the highest level at which no more than one subject experiences a DLT.
The number of subjects who have at least one serious adverse event related to the study.
All subjects who receive study drug will be closely monitored for serious adverse events (SAEs). The NCI's CTCAE (Common Toxicity Criteria for Adverse Effects) v4.03 will be used.
Overall survival
The number of subjects alive at two years from the first day of salvage therapy.
Secondary Outcome Measures
The number of subjects with a complete response (CR).
A complete response will be defined as bone marrow blasts <5% with absolute neutrophil count ≥1000/μL and platelet ≥100,000/μL.
The number of subjects with CR with incomplete hematologic recovery (CRi)
CRi is defined as CR without platelet recovery or neutrophil recovery. This will be defined as bone marrow blasts <5% with absolute neutrophil count <1000/L and platelet <100,000/L.
The number of subjects in a morphologic leukemia-free state (MLFS).
MLFS is bone marrow blasts <5% with absolute neutrophil count <1000/μL AND platelet <100,000/μL.
The number of subjects experiencing partial remission.
Partial remission (PR) is defined by a decrease of at 50% or more in the percentage of blasts to less than 25% in the bone marrow. and normalized blood counts ( ANC>1000, Platelets>100,000/ml).
Progression-free Survival
The number of subjects, who from the first day of remission until one year, do not relapse or progress.
Full Information
NCT ID
NCT03441048
First Posted
February 15, 2018
Last Updated
October 18, 2022
Sponsor
Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT03441048
Brief Title
Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia
Official Title
A Phase I Study of Lintuzumab-Ac225 in Combination With CLAG-M Chemotherapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 22, 2018 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a prospective, single-center phase I clinical study aimed at determining the maximum-tolerated dose, recommended phase 2 dose and safety of Lintuzumab-Ac225 in combination with CLAG-M chemotherapy in the management of relapsed/refractory acute myeloid leukemia. This study uses a 3+3 design with a five-patient cohort at the recommended phase 2 dose.
Detailed Description
Relapsed/refractory acute myeloid leukemia (RR-AML) in adults is an important therapeutic challenge. Nearly 60% of AML patients ultimately relapse or have refractory disease, and failure to achieve remission in this population is almost universally fatal. Therefore, a critical need exists for the development of novel therapies.
Currently, for RR-AML, many institutions utilize the chemotherapy regimen of CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) based on a reported morphological complete remission (CR) rate of 58% in prospective clinical trials. Because of this, and its favorable performance when compared with outcomes reported for other regimens utilized in RR-AML, we believe enhancing the efficacy of CLAG-M is a rational approach to improve therapy in RR-AML.
A promising approach that could enhance the clearance of leukemic blasts when added to CLAG-M chemotherapy is a monoclonal antibody radioconjugate directed against markers expressed in leukemic cells. Radiation has known cytotoxic properties in chemo-resistant AML. The benefit of an antibody radioconjugate would be leukemic specific delivery of potent radiotherapy with potentially minimal systemic off-target side-effects. One such antibody radioconjugate is Lintuzumab-Ac225, a highly cytotoxic alpha radiation emitter that targets the cluster of differentiation 33 (CD33) cell surface antigen, which is expressed on leukemic cells.
In this novel study, we aim to add the radioconjugated antibody Lintuzumab-Ac225 to salvage CLAG-M chemotherapy in order to improve the treatment response for patients with RR-AML.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute myeloid leukemia, Relapsed/refractory acute myeloid leukemia, CLAG-M, Lintuzumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lintuzumab Ac225 (Dose 1 - 0.25 μCi/kg Ac-225 with 1.6 μg/kg lintuzumab)
Arm Type
Experimental
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Arm Title
Lintuzumab Ac225 (Dose 2 - 0.50 μCi/kg Ac-225 with 3.2 μg/kg lintuzumab)
Arm Type
Experimental
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Arm Title
Lintuzumab Ac225 (Dose 3 - 0.75 μCi/kg Ac-225 with 4.7μg/kg lintuzumab)
Arm Type
Experimental
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Arm Title
Lintuzumab Ac225 (Dose 4 - 1.00 μCi/kg Ac-225 with 6.4 μg/kg lintuzumab)
Arm Type
Experimental
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Arm Title
Lintuzumab Ac225 (Dose 5 - 1.25 μCi/kg Ac-225 with 8.0 μg/kg lintuzumab)
Arm Type
Experimental
Arm Description
Dose escalation for lintuzumab-Ac225 will be conducted according to a 3+3 design. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Arm Title
Lintuzumab Ac225 Recommended Phase 2 Dose (RP2D)
Arm Type
Experimental
Arm Description
The maximum-tolerated dose for lintuzumab-Ac225 is defined as the highest level at which no more than one patient experiences a dose-limiting toxicity. The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Dose 1: 0.25 μCi/kg Ac-225 with 1.6 μg/kg lintuzumab)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of relapsed/refractory acute myeloid leukemia. Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Drug
Intervention Name(s)
Cladribine
Other Intervention Name(s)
Leustatin, Mavenclad
Intervention Description
Cladribine 5mg/m^2/day IV over two hours on days 2-6.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Cytosar-U, Depocyt, cytosine arabinoside (ara-C)
Intervention Description
Cytarabine 2 gm/m^2/day IV over four hours on days 2-6.
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Mitozantrone, Novantrone
Intervention Description
Mitoxantrone 10mg/m^2/day IV on days 2-4.
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
colony-stimulating factor 3 (CSF 3)
Intervention Description
G-CSF at a dose of 300 µg on days 1-6.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Dose 2: 0.50 μCi/kg Ac-225 with 3.2 μg/kg lintuzumab)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of relapsed/refractory acute myeloid leukemia. Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Dose 3: 0.75 μCi/kg with 4.7μg/kg lintuzumab)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of relapsed/refractory acute myeloid leukemia. Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Dose 4: 1.00 μCi/kg with 6.4 μg/kg lintuzumab)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of relapsed/refractory acute myeloid leukemia. Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Dose 5: 1.25 μCi/kg with 8.0 μg/kg lintuzumab)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
Lintuzumab-Ac225 is an immunoconjugate [antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)] for the treatment of relapsed/refractory acute myeloid leukemia. Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Intervention Type
Biological
Intervention Name(s)
Lintuzumab-Ac-225 (Recommended Phase 2 Dose)
Other Intervention Name(s)
HuM195-Ac225, Actimab-A
Intervention Description
The maximum-tolerated dose for lintuzumab-Ac225 is defined as the highest level at which no more than one patient experiences a dose-limiting toxicity. The RP2D is defined as the dose level below the dose where two or more dose-limiting toxicities were observed. CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m^2/day IV over two hours on days 2-6; cytarabine 2 gm/m^2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m^2/day IV on days 2-4 and G-CSF at a dose of 300 µg on days 1-6). Lintuzumab-Ac225 will be administered as a single dose on day 8 of therapy.
Primary Outcome Measure Information:
Title
The number of subjects with dose-limiting toxicities.
Description
Dose-escalation will be conducted according to a 3+3 design with a five-patient expansion cohort at the recommended phase 2 dose. The initial dose of Lintuzumab-Ac225 will be 0.25 micro-Curie (μCi)/kg (Dose level 1), and the highest dose administered will be 1.25 μCi/kg.
if 0/3 pts have no dose-limiting toxicity (DLT), new patients enter next dose level.
if 1/3 pts has DLT, 3 pts treated at same dose level.
if 0/3 pts at that dose level has DLT, new pts enter higher level.
if 1 or more of the additional 3 pts has a DLT, no further pts started at dose level, preceding dose is the MTD.
if 2/3 of initially dosed patients have a DLT on first dose, study terminated.
if 0/3 have DLT at highest dose, additional 3 enrolled.
Time Frame
28 Days
Title
Maximum-tolerated dose.
Description
Defined as the dosage with the highest level at which no more than one subject experiences a DLT.
Time Frame
28 Days
Title
The number of subjects who have at least one serious adverse event related to the study.
Description
All subjects who receive study drug will be closely monitored for serious adverse events (SAEs). The NCI's CTCAE (Common Toxicity Criteria for Adverse Effects) v4.03 will be used.
Time Frame
60 days
Title
Overall survival
Description
The number of subjects alive at two years from the first day of salvage therapy.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The number of subjects with a complete response (CR).
Description
A complete response will be defined as bone marrow blasts <5% with absolute neutrophil count ≥1000/μL and platelet ≥100,000/μL.
Time Frame
Up to Day 60
Title
The number of subjects with CR with incomplete hematologic recovery (CRi)
Description
CRi is defined as CR without platelet recovery or neutrophil recovery. This will be defined as bone marrow blasts <5% with absolute neutrophil count <1000/L and platelet <100,000/L.
Time Frame
Up to Day 60
Title
The number of subjects in a morphologic leukemia-free state (MLFS).
Description
MLFS is bone marrow blasts <5% with absolute neutrophil count <1000/μL AND platelet <100,000/μL.
Time Frame
Up to Day 60
Title
The number of subjects experiencing partial remission.
Description
Partial remission (PR) is defined by a decrease of at 50% or more in the percentage of blasts to less than 25% in the bone marrow. and normalized blood counts ( ANC>1000, Platelets>100,000/ml).
Time Frame
Up to Day 60
Title
Progression-free Survival
Description
The number of subjects, who from the first day of remission until one year, do not relapse or progress.
Time Frame
1 Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years at the time of informed consent.
Morphologically documented primary AML or secondary AML [from prior conditions such as Myelodysplastic Syndrome (MDS), myeloproliferative neoplasm (MPN)] or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
In first or subsequent relapse or refractory status after prior therapy, with or without prior hematopoietic stem cell transplant (HSCT). Patients with MDS and progression to AML on hypomethylating agents will also be included.
Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
Greater than 25% of blasts must be CD33 positive on flow cytometry using Phycoerythrin (PE) labeled anti-CD33 antibody.
Patients must meet the following clinical laboratory criteria:
Total bilirubin ≤ 2 x the upper limit of the normal range (ULN)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
Calculated creatinine clearance ≥ 50 mL/min
Resting left ventricular ejection fraction (LVEF) > 40%
Female patients must agree to avoid becoming pregnant, and male patients should avoid impregnating a female partner.
Exclusion Criteria:
Acute Promyelocytic Leukemia.
Active severe infection not well controlled by antibacterial or antiviral therapy.
Known infection with human immunodeficiency virus.
Patients with documented pulmonary disease, with a diffusing capacity of the lungs for carbon monoxide (DLCO) and/or forced expiratory volume in one second (FEV1) <65%, or history of dyspnea at rest, or requiring oxygen.
Pregnant or breast feeding women.
Prior chemotherapy or radiotherapy within 14 days of study entry unless fully recovered from adverse effects due to treatment, at investigator's discretion.
Active malignancy within 2 years of entry, except previously treated melanoma grade 2 or less, non-melanoma skin cancer, carcinoma in situ, or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of progressive disease based on prostate-specific antigen (PSA) levels and are not on active therapy. Active malignancy is malignancy receiving treatment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sameem Abedin, MD
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Froedtert Hospital and the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia
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