Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation

  • STATUS
    Recruiting
  • End date
    Dec 31, 2024
  • participants needed
    24
  • sponsor
    M.D. Anderson Cancer Center
Updated on 24 October 2022
cancer
remission
chronic myeloid leukemia
stem cell transplantation
graft versus host disease
myeloid leukemia
lymphoid leukemia
total body irradiation
fludarabine
hematologic malignancy
anemia
cyclophosphamide
chronic lymphocytic leukemia
lymphoma
multiple myeloma
hodgkin's disease
white blood cell count
ejection fraction
cytokines
cell transplantation
leukemia
bone marrow procedure
lymphocytic leukemia
gilbert's syndrome
antithymocyte globulin
myeloproliferative syndromes
white blood cells
progressive disease
chemotherapy regimen
follicular lymphoma
mantle cell lymphoma
pain management
aplastic anemia
blood cell count
lymphocyte immune globulin
Accepts healthy volunteers

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).

Description

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.

Details
Condition 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
Treatment anti-thymocyte globulin, cyclophosphamide, peripheral blood stem cell transplantation, Fludarabine, Total-Body Irradiation, Cytokine-treated Veto Cells
Clinical Study IdentifierNCT03622788
SponsorM.D. Anderson Cancer Center
Last Modified on24 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
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 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
Availability of a haploidentical related donor
Clinically significant neurologic event (stroke) or neurological deficit lasting > 24 hours
Karnofsky performance status >= 70%
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)
Left ventricular ejection fraction of at least 40%
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)
Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration
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
Serum creatinine =< 1.5 mg/dl
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)
Serum glutamic-pyruvic transaminase (SGPT) =< 200 IU/ml
Patients with hematological malignancies must have had persistent or progressive
Bilirubin < 1.5 mg/dl (unless Gilbert's syndrome)
disease despite initial chemotherapy and must have achieved stable disease or
Negative pregnancy test in a woman with child bearing potential
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

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
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