- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01619761
NK Cells in Cord Blood Transplantation
Natural Killer Cells in Allogeneic Cord Blood Transplantation
Study Overview
Status
Conditions
- Recurrent Hodgkin Lymphoma
- Refractory Hodgkin Lymphoma
- Secondary Acute Myeloid Leukemia
- Myelodysplastic Syndrome
- Recurrent Acute Myeloid Leukemia
- Recurrent Small Lymphocytic Lymphoma
- Refractory Chronic Lymphocytic Leukemia
- Recurrent Non-Hodgkin Lymphoma
- Refractory Non-Hodgkin Lymphoma
- Recurrent Acute Lymphoblastic Leukemia
- Refractory Acute Lymphoblastic Leukemia
- Therapy-Related Acute Myeloid Leukemia
- Therapy-Related Myelodysplastic Syndrome
- Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Acute Biphenotypic Leukemia
- Recurrent Chronic Lymphocytic Leukemia
- Refractory Small Lymphocytic Lymphoma
- DS Stage II Plasma Cell Myeloma
- DS Stage III Plasma Cell Myeloma
- Acute Myeloid Leukemia in Remission
- High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
- ISS Stage III Plasma Cell Myeloma
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Acute Lymphoblastic Leukemia in Remission
- ISS Stage II Plasma Cell Myeloma
Intervention / Treatment
- Other: Laboratory Biomarker Analysis
- Drug: Cyclophosphamide
- Biological: Rituximab
- Drug: Lenalidomide
- Drug: Melphalan
- Radiation: Total-Body Irradiation
- Biological: Natural Killer Cell Therapy
- Drug: Fludarabine Phosphate
- Drug: Tacrolimus
- Drug: Mycophenolate Mofetil
- Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
- Procedure: Umbilical Cord Blood Transplantation
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / 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.
|
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic umbilical cord blood transplant
Other Names:
Undergo allogeneic umbilical cord blood transplant
Other Names:
|
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.
|
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Undergo TBI
Other Names:
Given IV
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV or PO
Other Names:
Undergo allogeneic umbilical cord blood transplant
Other Names:
Undergo allogeneic umbilical cord blood transplant
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 1 year
|
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.
|
100 days
|
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.
|
Up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with acute graft-versus-host-disease
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Proportion of patients with chronic graft-versus-host-disease
Time Frame: Up to 1 year
|
Up to 1 year
|
|
Overall survival
Time Frame: 1 year
|
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
|
1 year
|
Disease-free survival
Time Frame: 1 year
|
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
|
1 year
|
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.
|
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
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.
|
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
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Precancerous Conditions
- Leukemia, B-Cell
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Hodgkin Disease
- Recurrence
- Lymphoma, Non-Hodgkin
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Leukemia, Myeloid, Accelerated Phase
- Leukemia, Biphenotypic, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Antibodies
- Lenalidomide
- Immunoglobulins
- Rituximab
- Melphalan
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Fludarabine
- Fludarabine phosphate
- Tacrolimus
- Mycophenolic Acid
- Mechlorethamine
- Nitrogen Mustard Compounds
Other Study ID Numbers
- 2011-0493 (OTHER: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2012-02071 (REGISTRY: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Recurrent Hodgkin Lymphoma
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin LymphomaUnited States
-
University of WashingtonRecruitingRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Recurrent Adult Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Follicular Lymphoma | Recurrent Lymphoplasmacytic Lymphoma | AIDS-Related Hodgkin LymphomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI); Merck Sharp & Dohme LLCActive, not recruitingLymphocyte-Rich Classical Hodgkin Lymphoma | Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma | Recurrent Mixed Cellularity Classical Hodgkin Lymphoma | Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma | Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma | Refractory Mixed... and other conditionsUnited States
-
National Cancer Institute (NCI)RecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous... and other conditionsUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)RecruitingDiffuse Large B-Cell Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Recurrent Waldenstrom... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)WithdrawnHIV Infection | Recurrent Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | AIDS-Related Non-Hodgkin Lymphoma | AIDS-Related Hodgkin LymphomaUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Adult Hodgkin Lymphoma | Refractory Childhood Hodgkin Lymphoma | Recurrent Childhood Hodgkin LymphomaUnited States, Canada
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRefractory Hodgkin Lymphoma | Recurrent Adult Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Prolymphocytic Leukemia | Refractory Chronic Lymphocytic Leukemia | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | T-Cell Chronic Lymphocytic Leukemia | Recurrent Childhood Non-Hodgkin... and other conditionsUnited States, Germany
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States