We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04620681
Recruitment Status : Recruiting
First Posted : November 9, 2020
Last Update Posted : September 28, 2022
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Secondary Acute Myeloid Leukemia Biological: CD8 Depleted, Non-engrafting,HLA mismatched unrelated donor lymphocytes Drug: Standard of Care Chemotherapy Phase 1 Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD8 Depleted, Non-Engrafting, HLA Mismatched Unrelated Donor Lymphocyte Infusion in Patients With MDA and Secondary AML
Actual Study Start Date : January 14, 2021
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : December 1, 2024


Arm Intervention/treatment
Experimental: Phase 1 Dose Level 1
All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 1: 1X10^6 CD4 T Cells/kg
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

Experimental: Phase 1 Dose Level 2
All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 2: 1X10^7 CD4 T Cells/kg
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

Experimental: Phase 1 Dose Level 3
All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at dose level 3: 5 X10^7 CD4 T Cells/kg
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

Experimental: Phase 2 -Treatment at Maximum Tolerated Dose (MTD)
All participants will receive cytotoxic induction chemotherapy with a standard of care cytarabine-based regimen. 24-36 hours after chemotherapy cessation, participants will receive CD8-depleted non-engrafting HLA-mismatched unrelated donor lymphocyte infusion (NE-DLI) at MTD.
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




Primary Outcome Measures :
  1. Maximum Tolerated Dose of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI) [ Time Frame: Up to 60 days per dose level ]
    Maximum Tolerated Dose will be determined by testing increasing doses of CD8 depleted non-engrafting HLA-mismatched unrelated donor lymphocytes infusion (NE-DLI).


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 12 months ]
    Overall Response Rate is defined as Complete Response + Partial Response using RECIST v1.1 criteria.

  2. Progression Free Survival [ Time Frame: Up to 12 months ]
    Progression Free Survival is defined as the time from enrollment to date of progression or death, or censor at last follow-up date.

  3. Overall Survival [ Time Frame: Up to 12 months ]
    Overall Survival is defined as the time from study enrollment to death from any cause or censored at last follow up date

  4. Hematologic Response [ Time Frame: Up to 12 months ]
    Hematologic response will be determined using International Working Group 2006 criteria for MDS patients and the International Working Group 2003 criteria for AML



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04620681


Locations
Layout table for location information
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Jeffrey Edelman    813-745-1040    Jeffrey.Edelman@moffitt.org   
Principal Investigator: Hany Elmariah, MD, MS         
Sub-Investigator: Nelli Bejanyan, MD         
Sub-Investigator: Marco Davila, MD, PhD         
Sub-Investigator: Farhad Khimani, MD         
Sub-Investigator: Rami Komrokji, MD         
Sub-Investigator: Andrew Kuykendall, MD         
Sub-Investigator: Jeffrey Lancet, MD         
Sub-Investigator: Eric Padron, MD         
Sub-Investigator: David Sallman, MD         
Sub-Investigator: Chetasi Talati, MD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Layout table for investigator information
Principal Investigator: Hany Elmariah, MD, MS Moffitt Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT04620681    
Other Study ID Numbers: MCC-20042
G6095 ( Other Grant/Funding Number: FDA )
First Posted: November 9, 2020    Key Record Dates
Last Update Posted: September 28, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
MDS
sAML
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Myelodysplastic Syndromes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Neoplastic Processes
Pathologic Processes