Brief Title
Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant
Official Title
Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation
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).
Detailed 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Optimal dose of donor-derived cytokine-treated veto cells
Secondary Outcome
Incidence of adverse events
Condition
Acute Lymphoblastic Leukemia
Intervention
Anti-Thymocyte Globulin
Study Arms / Comparison Groups
Treatment (chemotherapy, PBSCT, cytokine-treated veto cells)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
24
Start Date
August 8, 2019
Completion Date
December 1, 2025
Primary Completion Date
December 1, 2025
Eligibility Criteria
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 haploidentical related donor.
- 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 child bearing potential.
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.
Gender
All
Ages
12 Years - 75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Richard E Champlin, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03622788
Organization ID
2018-0221
Secondary IDs
NCI-2018-01557
Responsible Party
Sponsor
Study Sponsor
M.D. Anderson Cancer Center
Study Sponsor
Richard E Champlin, Principal Investigator, M.D. Anderson Cancer Center
Verification Date
March 2023