Lintuzumab-Ac225 in Combination With Cladribine + Cytarabine + Filgastrim + Mitoxantrone (CLAG-M) for Relapsed/Refractory Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, single-center phase I clinical study aimed at determining the maximum-tolerated 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 to estimate the maximum-tolerated dose (MTD).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical College of Wisconsin
• Treatments: Antibodies, Monoclonal; Cladribine; Cytarabine; Lenograstim; Lintuzumab; Mitoxantrone; Sargramostim

Criteria

Inclusion Criteria:

1. Age ≥18 years at the time of informed consent.

2. 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.

3. 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.

4. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.

5. Greater than 25% of blasts must be CD33 positive on flow cytometry using Phycoerythrin (PE) labeled anti-CD33 antibody.

6. 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%

7. Female patients must agree to avoid becoming pregnant, and male patients should avoid impregnating a female partner.

Exclusion Criteria:

1. Acute Promyelocytic Leukemia.

2. Active severe infection not well controlled by antibacterial or antiviral therapy.

3. Known infection with human immunodeficiency virus.

4. 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.

5. Pregnant or breast feeding women.

6. Prior chemotherapy or radiotherapy within 14 days of study entry unless fully recovered from adverse effects due to treatment, at investigator's discretion.

7. 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.