Status unknownNCT01619761Updated Feb 11, 2020

NK Cells in Cord Blood Transplantation

A Phase 1 interventional study of Allogeneic Hematopoietic Stem Cell Transplantation and Cyclophosphamide in Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia in Remission, sponsored by M.D. Anderson Cancer Center. Status unknown at 1 site in United States. Open to participants aged Up to 75 Years. Per ClinicalTrials.gov, last updated 2020-02-11.

Sponsored by M.D. Anderson Cancer Center · Phase 1, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Feb 2020), so the status shown — last known as Active, not recruiting — may be out of date.

Phase: Phase 1
Study type: Interventional
Enrollment: 13
Allocation: Non-randomized
Ages: Up to 75 Years
Sex: All

Study summary

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer 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.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of ex-vivo expanded cord blood (CB) natural killer (NK) cells with double CB transplantation in patients with hematological malignancies.

SECONDARY OBJECTIVES:

I. To monitor engraftment, chimerism, graft versus host disease, and immune reconstitution in patients receiving expanded CB NK cell therapy.

II. To estimate the time to platelet recovery and the time to absolute neutrophil count (ANC) recovery.

III. To estimate overall survival and disease free survival at one year. IV. To study the in-vivo persistence of cord blood NK cells.

OUTLINE:

PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 treatment plans:

TREATMENT PLAN 1: Patients receive high-dose lenalidomide orally (PO) once daily (QD) on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab intravenously (IV) over 6 hours on days -8 to -4.

TREATMENT PLAN 2: Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo total body irradiation (TBI) on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.

NK CELL INFUSION: All patients receive ex-vivo expanded cord blood NK cells IV over 30 minutes on day -2.

TRANSPLANT: All patients undergo allogeneic umbilical cord blood transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: All patients receive tacrolimus IV or PO on days -2 to 180 followed by taper and mycophenolate mofetil IV over 2 hours or PO thrice daily (TID) on days -3 to 100.

After completion of study treatment, patients are followed up at 3, 6, and 12 months.

Conditions studied

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Acute Biphenotypic Leukemia
Acute Lymphoblastic Leukemia in Remission
Acute Myeloid Leukemia in Remission
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
ISS Stage II Plasma Cell Myeloma
ISS Stage III Plasma Cell Myeloma
Myelodysplastic Syndrome
Recurrent Acute Lymphoblastic Leukemia
Recurrent Acute Myeloid Leukemia
Recurrent Chronic Lymphocytic Leukemia
Recurrent Hodgkin Lymphoma
Recurrent Non-Hodgkin Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Acute Lymphoblastic Leukemia
Refractory Chronic Lymphocytic Leukemia
Refractory Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
Refractory Small Lymphocytic Lymphoma
Secondary Acute Myeloid Leukemia
Therapy-Related Acute Myeloid Leukemia
Therapy-Related Myelodysplastic Syndrome

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In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 13 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.

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Lead sponsor

M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.

Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Up to 75 Years
Sexes eligible: All
Accepts healthy volunteers: No

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, 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 syndrome, any disease beyond first remission
Myelodysplastic syndrome (MDS): primary or therapy related
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 t(9;22) or t(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, refractory NHL, or relapsed NHL (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease
Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; patients with progressive CLL following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell transplantation; this includes patients with (1) lack of response or early relapse within 1 year of receiving a purine analog-containing treatment regimen, (2) disease relapse within 2 years of receiving a purine analog combination therapy or after other therapies such as autologous stem cell transplantation, and (3) CLL associated with tumor protein (p)53 mutations or deletions and/or deletion (del) (17p) requiring therapy; patients must have chemosensitive disease with at least a partial response (PR) or stable disease (SD) with last treatment regimen
Chronic myeloid leukemia (CML) second chronic phase or accelerated phase
Hodgkin's disease (HD): induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)
Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
Left ventricular ejection fraction greater than 45%
Pulmonary function test (PFT) demonstrating a diffusion capacity of least 45% predicted
Creatinine \< 1.6 mg/dL
Serum glutamate pyruvate transaminase (SGPT) =\< to 2.0 x normal
Bilirubin =\< to 2.0 x normal
All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS program
Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 24 months or no previous surgical sterilization and willing to ongoing pregnancy testing while on treatment with lenalidomide
Woman with child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide
Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy
Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular) antigens; each cord must contain at least 1.5 x 10\^7 total nucleated cells/Kg recipient body weight (pre-thaw); cord blood units will be procured through the National Marrow Donor Program (NMDP)
Have identified a backup cells source in case of engraftment failure; the source can be autologous, related or unrelated
Patients who have had a prior autologous transplant are eligible

Exclusion criteria

Exclusion Criteria:

Patients with known history of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
Active central nervous system (CNS) disease in patient with history of CNS malignancy
Patients with chronic active hepatitis or cirrhosis; if positive hepatitis serology, the study chair may deem the patient eligible based on the results of liver biopsy
Patients with known hypersensitivity to lenalidomide and/or rituximab
Patients who have a matched related donor who is eligible and willing to donate stem cells

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 13 participants (actual)

Study arms

Experimental
Treatment Plan 1 (NK cells, umbilical cord blood transplant)
Patients receive high-dose lenalidomide PO QD on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab IV over 6 hours on days -8 to -4.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Lenalidomide · Drug: Melphalan · Drug: Mycophenolate Mofetil · Biological: Natural Killer Cell Therapy · Biological: Rituximab · Drug: Tacrolimus · Procedure: Umbilical Cord Blood Transplantation
Experimental
Treatment Plan 2 (NK cells, umbilical cord blood transplant)
Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo TBI on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Cyclophosphamide · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Drug: Lenalidomide · Drug: Mycophenolate Mofetil · Biological: Natural Killer Cell Therapy · Biological: Rituximab · Drug: Tacrolimus · Radiation: Total-Body Irradiation · Procedure: Umbilical Cord Blood Transplantation

Interventions

ProcedureAllogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic umbilical cord blood transplant
Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
DrugCyclophosphamide
Given IV
Also known as: (-)-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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
DrugFludarabine Phosphate
Given IV
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
OtherLaboratory Biomarker Analysis
Correlative studies
DrugLenalidomide
Given PO
Also known as: CC-5013, CC5013, CDC 501, Revlimid
DrugMelphalan
Given IV
Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813
DrugMycophenolate Mofetil
Given IV or PO
Also known as: Cellcept, MMF
BiologicalNatural Killer Cell Therapy
Given IV
BiologicalRituximab
Given IV
Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83
DrugTacrolimus
Given IV or PO
Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic
RadiationTotal-Body Irradiation
Undergo TBI
Also known as: Total Body Irradiation, Whole-Body Irradiation
ProcedureUmbilical Cord Blood Transplantation
Undergo allogeneic umbilical cord blood transplant
Also known as: Cord Blood Transplantation, UCB transplantation

What researchers measure

Primary outcomes

Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate)
Will be estimated with 90% credible interval.
Time frame: Up to 1 year
Treatment-related mortality
The method described by Thall, et al will be used. Will be estimated with 90% credible interval. The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 100 days
Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Changes from baseline in vital signs and laboratory values will be summarized. Tabulate adverse events by severity and relationship to therapy.
Time frame: Up to 1 year

Secondary outcomes

Proportion of patients with acute graft-versus-host-disease
Time frame: Up to 1 year
Proportion of patients with chronic graft-versus-host-disease
Time frame: Up to 1 year
Overall survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 1 year
Disease-free survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 1 year
Time to initial platelet recovery
Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.
Time frame: From the infusion of peripheral blood stem cells to the first of 3 consecutive platelet count measurements tested on different days with a count greater than or equal to 20 x 10e9/L, assessed up to 1 year
Time to initial absolute neutrophil count recovery
Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.
Time frame: From the infusion of peripheral blood stem cells to the first of 3 consecutive days of an absolute neutrophil count greater than or equal to 0.5 x 10e9/L, assessed up to 1 year

Study locations

1 site

M D Anderson Cancer Center
Houston, Texas 77030, United States

References and documents

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 11, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01619761
Lead sponsor: M.D. Anderson Cancer Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jun 14, 2012
Start date: May 3, 2013
Primary completion: Nov 2021 (estimated)
Completion: Nov 2021 (estimated)
Last update: Feb 11, 2020

Study contacts

Chitra Hosing

principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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