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NK Cells in Cord Blood Transplantation

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ClinicalTrials.gov Identifier: NCT01619761
Recruitment Status : Recruiting
First Posted : June 14, 2012
Last Update Posted : July 12, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
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 Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Lenalidomide Drug: Melphalan Drug: Mycophenolate Mofetil Biological: Natural Killer Cell Therapy Biological: Rituximab Drug: Tacrolimus Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Natural Killer Cells in Allogeneic Cord Blood Transplantation
Actual Study Start Date : May 3, 2013
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
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
Undergo allogeneic umbilical cord blood transplant
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Drug: Melphalan
Given IV
Other Names:
  • 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

Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF

Biological: Natural Killer Cell Therapy
Given IV

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Procedure: Umbilical Cord Blood Transplantation
Undergo allogeneic umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB 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
Undergo allogeneic umbilical cord blood transplant
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Drug: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF

Biological: Natural Killer Cell Therapy
Given IV

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation

Procedure: Umbilical Cord Blood Transplantation
Undergo allogeneic umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation




Primary Outcome Measures :
  1. Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate) [ Time Frame: Up to 1 year ]
    Will be estimated with 90% credible interval.

  2. Treatment-related mortality [ Time Frame: 100 days ]
    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.

  3. Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]
    Changes from baseline in vital signs and laboratory values will be summarized. Tabulate adverse events by severity and relationship to therapy.


Secondary Outcome Measures :
  1. Proportion of patients with acute graft-versus-host-disease [ Time Frame: Up to 1 year ]
  2. Proportion of patients with chronic graft-versus-host-disease [ Time Frame: Up to 1 year ]
  3. Overall survival [ Time Frame: 1 year ]
    The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

  4. Disease-free survival [ Time Frame: 1 year ]
    The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

  5. Time to initial platelet recovery [ 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 ]
    Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.

  6. Time to initial absolute neutrophil count recovery [ 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 ]
    Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01619761


Contacts
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Contact: Chitra M. Hosing, MD 713-792-8750 cmhosing@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Chitra Hosing    713-792-8750      
Principal Investigator: Chitra Hosing         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Chitra Hosing M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01619761     History of Changes
Other Study ID Numbers: 2011-0493
NCI-2012-02071 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2011-0493 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: July 12, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Blood Protein Disorders
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Accelerated Phase
Leukemia, Biphenotypic, Acute
Myelodysplastic Syndromes
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases