Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant

NCT03622788 | Active Not Recruiting Phase 1 FDA Drug FDA Device

• 2 other identifiers: 2018-0221NCI-2018-01557
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies how well cytokine-treated veto cells work in treating patients with hematologic malignancies following stem cell transplant. Giving chemotherapy and total-body irradiation before a stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Cytokine-treated veto cells may help the transplanted donor cells to develop and grow in recipients without causing graft-versus-host-disease (GVHD - when transplanted donor tissue attacks the tissues of the recipient's body).

Conditions

Acute Myeloid Leukemia; Aplastic Anemia; Bone Marrow Failure; Chronic Lymphocytic Leukemia; Follicular Lymphoma; Hodgkin Lymphoma; Mantle Cell Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (2)

• Optimal dose of donor-derived cytokine-treated veto cells

  For the purpose of dose-finding, toxicity is defined as steroid resistant grade 3 or 4 graft-versus-host-disease (GVHD), or death from any cause, within 42 days of veto cell infusion.

  Within 42 days of cytokine-treated veto cell infusion

• Efficacy of veto cells

  Efficacy is defined as the patient being alive and engrafted at day 42 post veto cell infusion.

  At day 42 post cytokine-treated veto cell infusion

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 1 year

• Response rate

  Up to 1 year

• Time to progression

  Up to 1 year

• Infections

  Up to 1 year

• Immune reconstitution

  Up to 1 year

Study Arms (1)

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive ATG IV over 4 hours on days -9 to -7, and fludarabine IV over 1 hour on days -6 to -3, then undergo TBI on day -1. TRANSPLANT: Patients undergo PBSCT IV over 30-60 minutes on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days +3 and +4 and cytokine-treated veto cells IV over 30-60 minutes on day +7.

Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Biological: Cytokine-treated Veto Cells; Drug: Fludarabine; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Total-Body Irradiation

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATS

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Cytokine-treated Veto Cells BIOLOGICAL

Given IV

Also known as: Activated Veto Cells, Activated Veto T-cells, Veto CD8-positive T-cells, Veto Cell, Veto Cells, Veto-enhanced CTL, Veto-enhanced Cytotoxic T-cell

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 12-75 years. The first 3 subjects will be 18 years of age to gain experience and observe safety. After 3 adult subjects have successfully engrafted and if the safety profile is tolerable, adolescents age 12 may be enrolled on to the trial
• Patients with a diagnosis either follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), Hodgkin's lymphoma (HL), non-Hodgkin's lymphoma (NHL), chronic myeloid leukemia (CML), myelodysplastic syndrome, myeloproliferative syndromes (MPD), acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).
• Patients with aplastic anemia and severe immune deficiency or nonmalignant bone marrow failure states. Patients with severe thalassemia requiring regular blood transfusions or sickle cell disease with severe clinical features (these include any clinically significant sickle genotype, for example, hemoglobin SS (Hb SS), hemoglobin SC (Hb SC), hemoglobin S beta thalassemia (Hb Sbeta), or Hemoglobin S-OArab genotype\] with at least one of the following manifestations:
• Clinically significant neurologic event (stroke) or neurological deficit lasting \> 24 hours;
• History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment or referral despite adequate supportive care measures (i.e. asthma therapy);
• An average of three or more pain crises per year in the 2-year period preceding enrollment or referral (required intravenous pain management in the outpatient or inpatient hospital setting);
• Administration of regular red blood cell (RBC) transfusion therapy, defined as 8 or more transfusion events per year (in the 12 months before enrollment) to prevent vaso-occlusive clinical complications (i.e. pain, stroke, or acute chest syndrome);
• An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity \>= 2.7 m/sec.
• Ongoing high impact1 chronic pain on a majority of days per month for \>= 6 months as defined as ONE or more of the following: Chronic pain without contributory sickle cell disease (SCD) complications2, OR mixed pain type in which chronic pain is occurring at site(s) (arms, back, chest, or abdominal pain) unrelated to any sites associated with contributory SCD complications2 (e.g. leg ulcers and/or avascular necrosis)
• Patients with hematological malignancies must have had persistent or progressive disease despite initial chemotherapy and must have achieved stable disease or a partial or complete response to their most recent chemotherapy. Patients with low bulk or indolent relapse are eligible without additional treatment. Patients with high-risk acute myeloid leukemia by European LeukemiaNet (ELN) criteria in first remission are eligible.
• Availability of a medically acceptable haploidentical related donor, age 12-70 years.
• Karnofsky performance status \>= 70%.
• Left ventricular ejection fraction of at least 40%.
• Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration.
• Serum creatinine =\< 1.5 mg/dl.

You may not qualify if:

• Human immune deficiency virus (HIV) seropositive.
• Uncontrolled infection or serious medical or psychiatric condition that would limit tolerance to the protocol treatment.
• Active central nervous system (CNS) malignancy.
• Availability of medically eligible, human leukocyte antigen (HLA)-matched related stem cell donor.
• Medically acceptable haploidentical donor age 12-70 years.
• Hemoglobin \> 12.0 g/dL \[female\] or \> 13.0 g/dL \[male\] or \> 11.0 g/dL for females of childbearing potential with documented iron deficiency anemia
• Platelet count 150, 0000/ul
• WBC 3.0 - 11.0 K/ul
• No anomalies on CBC and differential indicating a hematopoietic disorder
• Negative pregnancy test for women of childbearing potential; Not lactating
• Systolic blood pressure \< 170 mmHg and Diastolic blood pressure \< 95 mmHg
• Performance status KPS \> 70%
• CXR negative for active infection or malignancy
• EKG not suggestive of uncontrolled cardiac disease
• No known allergy to cytokines if cytokines are to be used.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Anemia, Aplastic; Bone Marrow Failure Disorders; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Follicular; Hodgkin Disease; Lymphoma, Mantle-Cell; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Multiple Myeloma

Interventions

Antilymphocyte Serum; Cyclophosphamide; fludarabine; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Anemia; Bone Marrow Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Study Officials

• Richard E Champlin

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 9, 2018
• Study Start: August 8, 2019
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)