Personalized NK Cell Therapy after Chemotherapy and Cord Blood Transplant in Treating Patients with Myelodysplastic Syndrome, Leukemia, Lymphoma or Multiple Myeloma
This phase II clinical trial studies how well personalized natural killer (NK) cell therapy works after chemotherapy and umbilical cord blood transplant in treating patients with myelodysplastic syndrome, leukemia, lymphoma or multiple myeloma. This clinical trial will test cord blood (CB) selection for human leukocyte antigen (HLA)-C1/x recipients based on HLA-killer-cell immunoglobulin-like receptor (KIR) typing, and adoptive therapy with CB-derived NK cells for HLA-C2/C2 patients. Natural killer cells may kill tumor cells that remain in the body after chemotherapy treatment and lessen the risk of graft versus host disease after cord blood transplant.
Inclusion Criteria
- Patients must have one of the following hematologic malignancies: * Acute Myelogenous Leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics including complex karyotype, abn(3q), -5/5q-, -7/7q-, abn(12p), abn(17p), MLL gene re-arrangement and t (6;9), flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), history of central nervous system (CNS) disease, primary refractory disease or refractory disease after 2 or more lines of systemic therapy, secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), any disease beyond first remission * Myelodysplastic syndrome (MDS): Primary or therapy related, including patients that will be considered for transplant; these include any of the following categories: 1) revised International Prognostic Scoring System (IPSS) intermediate and high risk groups, 2) malondialdehyde (MDA) with transfusion dependency, 3) failure to respond or progression of disease on hypomethylating agents, 4) refractory anemia with excess of blasts, 5) transformation to acute leukemia, 6) chronic myelomonocytic leukemia, 7) atypical MDS/myeloproliferative syndromes, 8) complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p) * Acute Lymphoblastic Leukemia (ALL): Induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease, primary refractory disease or refractory disease after 2 or more lines of systemic therapy, or history of CNS disease. Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma * Non-Hodgkin's lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); relapsed double hit lymphomas; patients with options for treatment that are known to be curative are not eligible * Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following a minimum of two lines of standard therapy * CML second chronic phase or accelerated phase, history of CNS disease, or primary refractory disease or refractory disease after 2 or more lines of systemic therapy * Hodgkin's disease (HD): Induction failures, after first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease * Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment * A person (such as a haploidentical family member) or unit of cord blood must be identified as a source of back-up cells source in case of engraftment failure
- Patients Weight and Age Criteria * Weight >= 20 kg and =< 45 years (myeloablative regimen 1) * Weight >= 20 kg and =< 80 years (nonmyeloablative regimen 2) at the discretion of the investigator(s) * Weight >= 20 kg and =< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy may receive reduced intensity regimen 3
- Performance score of at least 60% by Karnofsky
- Left ventricular ejection fraction of at least 40% (myeloablative regimen 1, reduced intensity regimen 3)
- Left ventricular ejection fraction of at least 30% (nonmyeloablative regimen 2)
- Pulmonary function test (PFT) demonstrating an adjusted diffusion capacity of least 50% predicted value for hemoglobin concentration (myeloablative regimen 1, reduced intensity regimen 3)
- Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or glomerular filtration rate [GFR]) > 40mL/min/1.73 m^2
- Serum glutamate pyruvate transaminase (SGPT)/bilirubin < to 2.0 x normal (myeloablative regimen 1), reduced intensity regimen 3; SGPT/bilirubin < to 4.0 x normal (nonmyeloablative regimen 2)
- Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months
- Patients with options for treatment that are known to be curative are not eligible
- Patients with cognitive impairments who have a legally authorized representative that can sign consent are eligible
- English and non-English speaking patients are eligible
- Patients enrolled in this study may be enrolled on other supportive care investigational new drug (IND) studies at the discretion of the principal investigator (PI)
Exclusion Criteria
- Human immunodeficiency virus (HIV) positive; HIV results will be determined by nucleic acid testing
- Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which cord blood [CB] transplantation is proposed), or psychiatric condition that would limit informed consent
- Active central nervous system (CNS) disease in patient with history of CNS malignancy
- Availability of appropriate, willing, human leukocyte antigen (HLA)-matched related stem cell donor
Additional locations may be listed on ClinicalTrials.gov for NCT02727803.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVE:
I. Progression-free survival (PFS) time.
SECONDARY OBJECTIVES:
I. Overall survival (OS) time.
II. Transplant related mortality (TRM).
III. Graft versus host disease (GVHD).
IV. Infection.
OUTLINE: Patients are assigned to 1 of 5 preparative regimens.
MYELOABLATIVE REGIMEN 1: Patients receive anti-thymocyte globulin intravenously (IV) over 4 hours on days -9 and -8, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -7 to -4. Patients undergo total body irradiation (TBI) on day -3.
NON-MYELOABLATIVE REGIMEN 2: Patients with cluster of differentiation (CD)20 positive malignancies receive rituximab IV over 6 hours on day -9. Patients receive anti-thymocyte globulin IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 1 hour on days -6 to -3, and cyclophosphamide IV over 3 hours on day -6 and undergo TBI on day -1 at the discretion of the investigator(s).
REDUCED INTENSITY REGIMEN 3: Patients receive anti-thymocyte globulin IV over 4 hours on days -7 and -6, fludarabine phosphate IV over 1 hour on days -5 to -2, and melphalan IV over 30 minutes on day -2.
TBI/FLUDARABINE/CYCLOPHOSPHAMIDE REGIMEN 4: Patients receive fludarabine and cyclophosphamide IV, and undergo TBI on study.
REDUCED INTENSITY REGIMEN 5: Patients receive fludarabine IV over 1 hour on days -6 to -2, cyclophosphamide IV over 3 hours on day -6, thiotepa IV over 4 hours on days -5 and -4. Patients undergo TBI on days -2 and -1.
UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0.
NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180.
Additionally, patients undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 1, 7, 14, 28, 45, 60, and 100 days, and at 6, 9, and 12 months, and then yearly for up to 4 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorAmanda L. Olson
- Primary ID2015-0313
- Secondary IDsNCI-2016-00584
- ClinicalTrials.gov IDNCT02727803