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

NCT ID: NCT03622788

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-08

Study Completion Date

2027-12-01

Brief Summary

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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).

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine the optimal dose of anti-viral veto cells, defined as the dose which achieves engraftment without severe graft-vs-host disease (GVHD) at 42 days after non-myeloablative megadose T cell depleted haploidentical hematopoietic cell transplantation (HCT).

SECONDARY OBJECTIVES:

I. Toxicity. II. Response rate. III. Time to progression. IV. Infections. V. Immune reconstitution. VI. Overall survival up to 1 year.

OUTLINE: This is a dose-escalation study of cytokine-treated veto cells.

CONDITIONING REGIMEN: Patients receive anti-thymocyte globulin (ATG) intravenously (IV) over 4 hours on days -9 to -7 and fludarabine IV over 1 hour on days -6 to -3, then undergo total body irradiation (TBI) on day -1.

TRANSPLANT: Patients undergo peripheral blood stem cell transplantation (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.

After completion of stem cell transplant, patients are followed up once a week for 4 weeks, once a month for 3 months, and then periodically for one year.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

Anti-Thymocyte Globulin

Intervention Type BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Cytokine-treated Veto Cells

Intervention Type BIOLOGICAL

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo PBSCT

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Interventions

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Anti-Thymocyte Globulin

Given IV

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Cytokine-treated Veto Cells

Given IV

Intervention Type BIOLOGICAL

Fludarabine

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo PBSCT

Intervention Type PROCEDURE

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Other Intervention Names

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Antithymocyte Globulin Antithymocyte Serum ATG ATS (-)-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 Activated Veto Cells Activated Veto T-cells Veto CD8-positive T-cells Veto Cell Veto Cells Veto-enhanced CTL Veto-enhanced Cytotoxic T-cell Fluradosa 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 SCT_TBI TBI Total Body Irradiation Whole Body Irradiation Whole-Body Irradiation

Eligibility Criteria

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Inclusion Criteria

* 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.
* Serum glutamic-pyruvic transaminase (SGPT) =\< 200 IU/ml.
* Bilirubin \< 1.5 mg/dl (unless Gilbert's syndrome).
* Negative pregnancy test in a woman with childbearing potential.


* 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.
* No active or uncontrolled autoimmune disorders
* Completion and signature of donor questionnaire (within 30 days)
* Donor infectious disease panel and health assessment performed by attending physician

Exclusion Criteria

* 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.


* Individuals with cognitive impairments and/or any serious unstable pre-existing condition or psychiatric disorder that can interfere with safety or without obtaining informed consent or compliance with study procedures.
Minimum Eligible Age

12 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Richard E Champlin

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

M D Anderson Cancer Center

Other Identifiers

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NCI-2018-01557

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0221

Identifier Type: OTHER

Identifier Source: secondary_id

2018-0221

Identifier Type: -

Identifier Source: org_study_id