Personalized NK Cell Therapy in CBT

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Personalized NK Cell Therapy in CBT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02727803
• Other study ID #: 2015-0313
• Secondary ID: NCI-2016-0058420
• Status: Recruiting
• Phase: Phase 2
• Start date: May 19, 2016
• Est. completion date: May 31, 2025

Study information

• Verified date: June 2024
• Source: M.D. Anderson Cancer Center
• Contact: Amanda Olson, MD
• Email: alolson[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

PRIMARY OBJECTIVES:

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 3 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 80 Years

Eligibility

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, abnormal [abn][3q], -5/5q-, -7/7q-, abn[12p], abn[17p], myeloid/lymphoid or mixed-lineage leukemia [MLL] gene re-arrangement and t [6;9]47, fms related tyrosine kinase 3 [flt3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndromes (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; 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

• Chronic myeloid leukemia (CML) second chronic phase or accelerated phase

• 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

• Patient age criteria: age >= 15 and =< 45 years (myeloablative regimen 1; age >= 15 and =< 80 years (nonmyeloablative regimen 2) at the discretion of the investigator(s); age >= 15 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 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

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Acute Biphenotypic Leukemia
• Acute Lymphoblastic Leukemia
• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia With Myelodysplasia-Related Changes
• Acute Myeloid Leukemia With Variant MLL Translocations
• Anemia, Refractory, with Excess of Blasts
• B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Chemotherapy-Related Leukemia
• Chronic Myelomonocytic Leukemia
• Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
• ISS Stage II Plasma Cell Myeloma
• ISS Stage III Plasma Cell Myeloma
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myeloid, Chronic-Phase
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndrome
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic Syndrome With Gene Mutation
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Previously Treated Myelodysplastic Syndrome
• Recurrence
• Recurrent Acute Myeloid Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Hodgkin Lymphoma
• Recurrent Non-Hodgkin Lymphoma
• Refractory Acute Lymphoblastic Leukemia
• Refractory Adult Acute Lymphoblastic Leukemia
• Secondary Acute Myeloid Leukemia
• Syndrome
• Therapy-Related Myelodysplastic Syndrome

Intervention

Biological:
• Allogeneic Natural Killer Cell Line NK-92
Given IV
• Anti-Thymocyte Globulin
Given IV

Drug:
• Busulfan
Given IV
• Clofarabine
Given IV
• Cyclophosphamide
Given IV
• Fludarabine Phosphate
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Melphalan
Given IV

Biological:
• Rituximab
Given IV

Radiation:
• Total-Body Irradiation
Undergo total body irradiation

Procedure:
• Umbilical Cord Blood Transplantation
Undergo umbilical cord blood transplantation

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS) time in C2C2 patients	Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, human leukocyte antigen (HLA) match, cytomegalovirus (CMV) status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	From the date of engraftment to disease progression or death, assessed up to 4 years
Primary	Progression free survival (PFS) time in C1 patients	Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	From the date of cord blood transplant to disease progression or death, assessed up to 4 years
Secondary	Overall survival time	Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	Up to 4 years
Secondary	Incidence of transplant related mortality	Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	Up to 4 years
Secondary	Incidence of graft-versus host disease	Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	Up to 4 years
Secondary	Incidence of infection	Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.	Up to 4 years

External Links

•   MD Anderson Cancer Center