Lintuzumab-Ac225 in Combination With CLAG-M Chemotherapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia
|ClinicalTrials.gov Identifier: NCT03441048|
Recruitment Status : Recruiting
First Posted : February 21, 2018
Last Update Posted : May 24, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Lintuzumab AC 225 Drug: Cladribine Drug: Cytarabine Drug: Mitoxantrone Drug: G-csf||Phase 1|
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 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Lintuzumab-Ac225 in Combination With CLAG-M Chemotherapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia|
|Actual Study Start Date :||May 22, 2018|
|Estimated Primary Completion Date :||April 1, 2019|
|Estimated Study Completion Date :||April 1, 2020|
Experimental: IV infusion of Lintuzumab AC225 following CLAG-M chemotherapy
CLAG-M chemotherapy will be administered at a fixed dose and schedule (cladribine 5mg/m2/day IV over two hours on days 2-6; cytarabine 2 gm/m2/day IV over four hours on days 2-6, starting two hours after the cladribine infusion is complete; mitoxantrone 10mg/m2/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 will be conducted according to a 3+3 design. The initial dose of Lintuzumab-Ac225 will be 0.25 uCi/kg (Dose level 1), and the highest dose administered will be 0.75uCi/kg.
Drug: Lintuzumab AC 225
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.
Cladribine 5mg/m2/day IV over two hours on days 2-6.
Cytarabine 2 gm/m2/day IV over four hours on days 2-6.
Mitoxantrone 10mg/m2/day IV on days 2-4.
G-CSF at a dose of 300 µg on days 1-6.
- Maximum-Tolerated Dose of Lintuzumab-AC225 [ Time Frame: Through primary study completion, 1 year ]
Dose-escalation will be conducted according to a 3+3 design. The initial dose of Lintuzumab-Ac225 will be 0.25 uCi/kg (Dose level 1), and the highest dose administered will be 0.75uCi/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.
- MTD = highest level at which no more than 1/6 experience a DLT.
- Toxicities of the Combination [ Time Frame: Through study completion, 2 years ]All patients who receive study drug will be closely monitored for adverse events (AEs). All AEs that occur during study period will be reported and the investigator will determine the severity and relationship to study drug (unrelated, unlikely, possibly, probably, or definitely related). The NCI's CTCAE(Common Toxicity Criteria for Adverse Effects)v4.03 will be used for grading AEs, in addition to a modified criteria for hematologic adverse events.
- Response Rates [ Time Frame: Through study completion, 2 years ]Assessment of response rates (complete, complete without platelet recovery, complete without platelet recovery or neutrophil recovery, partial and nonresponse) determined through bone marrow aspirate/biopsy and multi-color flow cytometry.
- Progression-free Survival [ Time Frame: Through study completion, 2 years ]Progression-free survival (PFS) will be calculated from the first day of remission until documentation of relapse/progression.
- Overall Survival [ Time Frame: Through study completion, 2 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03441048
|Contact: Medical College of Wisconsin Cancer Center Clinical Trials Officefirstname.lastname@example.org|
|United States, Wisconsin|
|Froedtert Hospital and the Medical College of Wisconsin||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|Contact: Cancer Center Clinical Trials Office 866-680-0505 ext 8900 email@example.com|
|Principal Investigator: Sameem Abedin, MD|
|Principal Investigator:||Sameem Abedin, MD||Medical College of Wisconsin|