NCT01619761

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
13

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2013

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 12, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 14, 2012

Completed
11 months until next milestone

Study Start

First participant enrolled

May 3, 2013

Completed
8.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2021

Completed
Last Updated

February 11, 2020

Status Verified

February 1, 2020

Enrollment Period

8.5 years

First QC Date

June 12, 2012

Last Update Submit

February 7, 2020

Conditions

Outcome Measures

Primary Outcomes (3)

  • 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.

    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.

    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.

    Up to 1 year

Secondary Outcomes (6)

  • Proportion of patients with acute graft-versus-host-disease

    Up to 1 year

  • Proportion of patients with chronic graft-versus-host-disease

    Up to 1 year

  • Overall survival

    1 year

  • Disease-free survival

    1 year

  • Time to initial platelet recovery

    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

  • +1 more secondary outcomes

Study Arms (2)

Treatment Plan 1 (NK cells, umbilical cord blood transplant)

EXPERIMENTAL

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 TransplantationDrug: Fludarabine PhosphateOther: Laboratory Biomarker AnalysisDrug: LenalidomideDrug: MelphalanDrug: Mycophenolate MofetilBiological: Natural Killer Cell TherapyBiological: RituximabDrug: TacrolimusProcedure: Umbilical Cord Blood Transplantation

Treatment Plan 2 (NK cells, umbilical cord blood transplant)

EXPERIMENTAL

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 TransplantationDrug: CyclophosphamideDrug: Fludarabine PhosphateOther: Laboratory Biomarker AnalysisDrug: LenalidomideDrug: Mycophenolate MofetilBiological: Natural Killer Cell TherapyBiological: RituximabDrug: TacrolimusRadiation: Total-Body IrradiationProcedure: Umbilical Cord Blood Transplantation

Interventions

Undergo allogeneic umbilical cord blood transplant

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

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
Treatment Plan 2 (NK cells, umbilical cord blood transplant)

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
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Correlative studies

Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

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
Treatment Plan 1 (NK cells, umbilical cord blood transplant)

Given IV or PO

Also known as: Cellcept, MMF
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Given IV

Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)
RituximabBIOLOGICAL

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
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation
Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Undergo allogeneic umbilical cord blood transplant

Also known as: Cord Blood Transplantation, UCB transplantation
Treatment Plan 1 (NK cells, umbilical cord blood transplant)Treatment Plan 2 (NK cells, umbilical cord blood transplant)

Eligibility Criteria

AgeUp to 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +7 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseLeukemia, Biphenotypic, AcuteLeukemia, Myeloid, Chronic-PhaseMyelodysplastic SyndromesPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteLeukemia, Lymphocytic, Chronic, B-CellHodgkin DiseaseLymphoma, Non-Hodgkin

Interventions

Cyclophosphamidefludarabine phosphateLenalidomideMelphalanMycophenolic AcidRituximabCT-P10TacrolimusWhole-Body IrradiationCord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsCaproatesAcids, AcyclicFatty AcidsLipidsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsSerum GlobulinsGlobulinsMacrolidesLactonesRadiotherapyTherapeuticsInvestigative TechniquesStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTransplantationSurgical Procedures, Operative

Study Officials

  • Chitra Hosing

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 12, 2012

First Posted

June 14, 2012

Study Start

May 3, 2013

Primary Completion

November 1, 2021

Study Completion

November 1, 2021

Last Updated

February 11, 2020

Record last verified: 2020-02

Locations