Clinical Trial · NCT02575963

Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients

Overview

The study is a multicenter, open label Phase I/II trial. 1. Establish the MTD of fractionated doses of Lintuzumab-Ac225 in combination with low dose cytosine arabinoside (Low Dose Ara-C, LDAC) (Phase 1 portion) 2. Determine the response rate (CR + CRp + CRi) to fractionated doses of Lintuzumab-Ac225 alone (Phase 2 portion)

Sponsor

Actinium Pharmaceuticals, Inc

Phase

Phase 1/2

Contacts

Avinash Desai, MD (STUDY_CHAIR)

ClinicalTrials.gov

NCT02575963

Eligibility

Inclusion

Greater than 25% of blasts must be CD33 positive.
Documented liver disease with marked elevation of transaminases \>3 x ULN or,
Creatinine \< 2.0 mg/dl
Greater than 25% of blasts must be CD33 positive.
Untreated AML, including patients with an antecedent hematologic disorder or secondary disease. Patients with prior MDS may have received therapy with immunomodulatory agents or hypomethylating agents for this diagnosis. Patients with other prior cancer diagnoses are allowed as long as they have no measurable disease, are not undergoing active therapy, and have a life expectancy of ≥ 4 months.
Blast count ≥20%
Documented pulmonary disease with DLCO ≤65% or FEV1 ≤65%, provided that patients do not require more than 2 L of oxygen per minute or,
Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or
Adequate renal and hepatic function
Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g. anthracycline and infusional cytarabine given as 7+3), or;
Untreated AML, including patients with an antecedent hematologic disorder or secondary disease. Patients with prior MDS may have received therapy with immunomodulatory agents for this diagnosis.
Patients ≥60 years unfit to receive intensive (e.g., 7+3) chemotherapy who have:
ECOG ≤ 3Phase 2 Inclusion Criteria:
Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g., anthracycline and infusional cytarabine given as 7+3); or
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or XRT, abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with FLT3-ITD, or presenting WBC\>100K, or
Estimated creatinine clearance ≥ 50ml/min
Bilirubin ≤ 2.0 mg/dl; AST and ALT \< 5.0 times the ULN
Serum creatinine \>1.2 mg/dL
Congestive heart failure or documented cardiomyopathy with an EF ≤50%, provided that EF ≥35% or,
Have a circulating blast count of less than 200/mm3 (control with hydroxyurea or similar agent is allowed);
Blast count ≥ 20% (WHO criteria)

Exclusion

Active serious infections uncontrolled by antibiotics
Active CNS leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache.
Treatment with chemotherapy or biologic therapy within 3 weeks, except for hydroxyurea, which must be discontinued prior to treatment on study
Treatment with radiation within 6 weeks
Psychiatric disorder that would preclude study participation
Patients with acute promyelocytic leukemia
Clinically significant cardiac or pulmonary disease
Patients with liver cirrhosis