Clinical Trials /

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

NCT02575963

Description:

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)

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients
  • Official Title: A Phase I/II Study of Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: API-01
  • NCT ID: NCT02575963
  • NCT ALIAS: NCT01756677

Conditions

  • AML

Interventions

DrugSynonymsArms
Cytarabine (Phase 1 only)Low dose Ara-C, LDACPhase 1 (Completed)
Lintuzumab-Ac225HuM195-Ac225, Actimab-APhase 1 (Completed)
Furosemide (Phase 1 only)LasixPhase 1 (Completed)
SpironolactoneAldactonePhase 1 (Completed)

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
Phase 1 (Completed)ExperimentalCytarabine + Lintuzumab-Ac225 Cytarabine days 1 to 10 of each cycle. Doses were divided into 2 equal fractions with the first fraction given approx. 4-7 days after 1 cycle of low dose cytarabine and the second fraction given 4-7 days after the first fraction, followed by up to 11 more cycles. Furosemide (Phase 1 only) and Spironolactone were administered after Lintuzumab-Ac225. Experimental: Phase 2 Experimental: Lintuzumab-Ac225 The Phase II dose determined during the Phase I dose escalation was 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8. Spironolactone is administered after Lintuzumab-Ac225.
  • Cytarabine (Phase 1 only)
  • Furosemide (Phase 1 only)
  • Spironolactone

Eligibility Criteria

        Phase 1 Major Inclusion Criteria:

          1. 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.

          2. Patients age ≥60 years who:

               1. Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or

               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

               3. 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;

               4. Any patient age ≥ 70 years.

          3. Blast count ≥20%

          4. Greater than 25% of blasts must be CD33 positive.

          5. Adequate renal and hepatic function

          6. ECOG ≤ 3

        Phase 2 Inclusion Criteria:

          1. 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.

          2. Patients age ≥60 years who:

               1. Patients ≥60 years unfit to receive intensive (e.g., 7+3) chemotherapy who have:

                    -  Congestive heart failure or documented cardiomyopathy with an EF ≤50%,
                       provided that EF ≥35% or,

                    -  Documented pulmonary disease with DLCO ≤65% or FEV1 ≤65%, provided that
                       patients do not require more than 2 L of oxygen per minute or,

                    -  Documented liver disease with marked elevation of transaminases >3 x ULN or,

                    -  Serum creatinine >1.2 mg/dL

               2. 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

               3. Any patient age ≥ 75 years.

          3. Blast count ≥ 20% (WHO criteria)

          4. Greater than 25% of blasts must be CD33 positive.

          5. Have a circulating blast count of less than 200/mm3 (control with hydroxyurea or
             similar agent is allowed);

          6. Creatinine < 2.0 mg/dl

          7. Estimated creatinine clearance ≥ 50ml/min

          8. Bilirubin ≤ 2.0 mg/dl; AST and ALT < 5.0 times the ULN

          9. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2

        Exclusion Criteria:

          1. Patients with acute promyelocytic leukemia

          2. Treatment with chemotherapy or biologic therapy within 3 weeks, except for
             hydroxyurea, which must be discontinued prior to treatment on study

          3. Treatment with radiation within 6 weeks

          4. Active serious infections uncontrolled by antibiotics

          5. Active malignancy within 2 years of entry, except previously treated non-melanoma skin
             cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ confined
             prostate cancer with no evidence of progressive disease based on PSA levels and are
             not on active therapy.

          6. Clinically significant cardiac or pulmonary disease

          7. Patients with liver cirrhosis

          8. 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.

          9. Psychiatric disorder that would preclude study participation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225
Time Frame:Cycle 1, up to 52 days
Safety Issue:
Description:If two or more patients in a cohort experience dose limiting toxicity (DLT), then maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. If only three patients were treated at a dose level under consideration as the MTD, then up to three additional patients will be accrued. If no more than one of the six patients at that dose level experiences DLT, then that dose level will be confirmed as the MTD.

Secondary Outcome Measures

Measure:Phase II: PFS
Time Frame:1 year
Safety Issue:
Description:Progression Free Survival
Measure:Phase II: LFS
Time Frame:1 year
Safety Issue:
Description:Leukemia Free Survival
Measure:Phase II: OS
Time Frame:1 year
Safety Issue:
Description:Overall Survival
Measure:Phase II: Toxicity Spectrum
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Actinium Pharmaceuticals

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