CD8 Depleted, Non-engrafting, HLA Mismatched Unrelated Infusion With MDS and Secondary AML

Myelodysplastic Syndromes Clinical Trial

Official title:

CD8 Depleted, Non-Engrafting, HLA Mismatched Unrelated Donor Lymphocyte Infusion in Patients With MDA and Secondary AML

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04620681
• Other study ID #: MCC-20042
• Secondary ID: G6095
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: January 14, 2021
• Est. completion date: August 10, 2024

Study information

• Verified date: February 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine the safety of an investigational treatment for myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine) stops working or after progression of MDS to acute myeloid leukemia (AML). Funding source - FDA OOPD.

Description:

The purpose of the study is to determine the safety of an investigational treatment for myelodysplastic syndrome (MDS) after the first therapy (such as azacitidine or decitabine) stops working or after progression of MDS to acute myeloid leukemia (AML).

Patients with advanced MDS are treated with hypomethylating agents (HMAs) such as azacitidine or decitabine. These medications can be effective for a few months to a few years, but usually lose effect eventually. This study is attempting to design a therapy called "non-engrafting, CD8 depleted donor lymphocyte infusion" or "NE-DLI" as a treatment for these diseases.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 19
• Est. completion date: August 10, 2024
• Est. primary completion date: August 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

Myelodysplastic Syndrome (MDS) having failed hypomethylating agent (HMA) therapy cohort:

• Age 18-79 years, inclusive

• Pathologically confirmed MDS or myelodysplastic/myeloproliferative overlap (MDS/MPN)

• IPSS-R score intermediate, high or very high

• Must have failed therapy with an HMA (defined as lack of response by International Working Group criteria (1) or intolerance of the drug)

Secondary Acute Myeloid Leukemia (sAML):

• Pathologically confirmed AML according to World Health Organization (WHO) criteria

• Evidence of an antecedent hematologic disorder (AHD) prior to acute leukemia including a known prior diagnosis of MDS, MPN or MDS/MPN or data suggestive of an AHD such as cytopenias, fibrosis, macrocytic anemia, cellular or dysplasia at or prior to the time of diagnosis. If available, MDS-defining karyotypes (-7/del(7q), -5/del(5q), del(13q), del(11q), del(12p), t(12p), del(9q), idic(X)(q13), t(17p) (unbalanced translocations) or i(17q) (ie, loss of 17p), t(11;16)(q23;p13.3), t(3;21)(q26.2;q22.1), t(1;3)(p36.3;q21), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)) or somatic mutations in multiple genes including p53, TET2, JAK2, CALR, MPL, ASXL1, RUNX1, SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 would also confirm eligibility.

• Age 60-79 years, inclusive

• May be previously untreated

For both cohorts:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Deemed eligible to receive cytotoxic chemotherapy

• Creatinine clearance (CrCl)>50ml/min

• Total bilirubin <2 mg/dL (except for patients with Gilbert's disease), AST and ALT < 3x ULN

• Left Ventricular Ejection Fraction = 50%

• Willing and able to participate in study assessments

Exclusion Criteria:

• Patients who have had systemic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Hydroxyurea during this period may be given as a bridging therapy to maintain disease stability while awaiting treatment. Intrathecal chemotherapy within this time frame is permitted. Intrathecal chemotherapy may be continued during protocol therapy in order to consolidate or maintain a central nervous system (CNS) remission, but not to treat active CNS disease

• Acute promyelocytic leukemia, or the presence of t(15;17)

• Patients receiving any other investigational agents

• Uncontrolled concurrent illness including, but not limited to, ongoing and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the fetus. Breastfeeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study

• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up

• Patients with a poor functional status of ECOG 3-4, or otherwise deemed unfit to tolerate induction chemotherapy.

• Patients with blastic transformation of chronic myelogenous leukemia are ineligible

• Exposure to a humanized mouse chimeric antibody, as this could sensitize patients to components of the CD8 depletion column that may be present in small amounts in the cell product

• Prior allogenic hematopoietic cell transplant

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Neoplasm Metastasis
• Secondary Acute Myeloid Leukemia

Intervention

Biological:
• CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes
Infusion of mononuclear cells, apheresis products depleted of CD8+ T cells using the CliniMACS® system with CliniMACS® CD8 reagent

Drug:
• Standard of Care Chemotherapy
Standard of care cytarabine-based chemotherapy

Locations

Country	Name	City	State
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI)	Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).	Up to 60 days per dose level
Secondary	Overall Response Rate	Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.	Up to 12 months
Secondary	Progression Free Survival	Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.	Up to 12 months
Secondary	Overall Survival	Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date	Up to 12 months
Secondary	Hematologic Response	Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML	Up to 12 months

External Links

•   Moffitt Cancer Center Clinical Trials website