Single or Double Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematologic Malignancies

This study has suspended participant recruitment.
(Funding unavailable)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier:
NCT01652014
First received: July 20, 2012
Last updated: June 28, 2013
Last verified: June 2013
  Purpose

This study will determine the safety and applicability of experimental forms of umbilical cord blood (UCB) transplantation for patients with high risk hematologic malignancies who might benefit from a hematopoietic stem cell transplant (HSCT) but who do not have a standard donor option (no available HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD)), or single UCB unit with adequate cell number and HLA-match).


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Blastic Phase Chronic Myelogenous Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Procedure: double-unit umbilical cord blood transplantation
Radiation: total-body irradiation
Drug: tacrolimus
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplantation Using Alternate Donor Umbilical Cord Blood Options

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Chronic Myeloproliferative Disorders Acute Lymphoblastic Leukemia Hodgkin Lymphoma Waldenstrom Macroglobulinemia Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic/myeloproliferative Disease Acute Myeloid Leukemia, Adult Follicular Lymphoma B-cell Lymphomas Burkitt Lymphoma Lymphoma, Large-cell Lymphomatoid Granulomatosis Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Anaplastic Large Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Peripheral T-cell Lymphoma Leukemia, T-cell, Chronic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Large Granular Lymphocyte Leukemia
U.S. FDA Resources

Further study details as provided by Rutgers, The State University of New Jersey:

Primary Outcome Measures:
  • Engraftment of white blood cells (WBC) (absolute neutrophil count > 500/mm^3) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Non-relapse mortality [ Time Frame: 40 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Platelet engraftment rate (non-transfusion dependent) [ Time Frame: At 100 days ] [ Designated as safety issue: No ]
  • Transplant related mortality [ Time Frame: At 1 year ] [ Designated as safety issue: Yes ]
  • Rates of infection requiring hospitalization or prolongation of hospitalization [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Incidence of steroid-refractory acute GVHD [ Time Frame: at 100 days ] [ Designated as safety issue: Yes ]
    GVHD will be staged per standard guidelines of the American Society for Blood and Bone Marrow Transplantation.

  • Incidence of extensive chronic GVHD [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
    GVHD will be staged per standard guidelines of the American Society for Blood and Bone Marrow Transplantation.

  • Total time on immunosuppressive therapy [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to CD4 count > 200/mm^3 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 38
Study Start Date: January 2014
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Double UCB transplantation

Patients receive conditioning comprising fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV over 1 hour on day -6, and undergo TBI on day -1. Patients also receive GVHD prophylaxis comprising tacrolimus IV continuously or PO beginning on day -3 with taper and mycophenolate mofetil PO BID days 1-30. Patients undergo double allogeneic UCB transplant on day 0.

Drug: cyclophosphamide
Given IV over 1 hour on Day -6; after pre-hydration
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: fludarabine phosphate
Given IV daily over 30 minutes for 5 days (Days -6 to -2)
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: mycophenolate mofetil
Given PO 1.0 g BID Day 1-30
Other Names:
  • Cellcept
  • MMF
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo double-unit allogeneic UCB transplant
Procedure: double-unit umbilical cord blood transplantation
Undergo double-unit allogeneic UCB transplant
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: tacrolimus
Given IV 0.03 mg/kg/d as continuous infusion over 24 hours starting Day -3 with dose adjustments to maintain level of 8-20 mg/ml
Other Names:
  • FK 506
  • Prograf
Experimental: Arm II

Sub-threshold single UCB + irradiated PBMCs transplantation

Patients receive conditioning comprising fludarabine phosphate IV over 30 minutes on days -6 to -2, cyclophosphamide IV over 1 hour on day -6, and undergo TBI on day -1. Patients also receive GVHD prophylaxis comprising tacrolimus IV continuously or PO beginning on day -3 with taper and mycophenolate mofetil PO BID days 1-30. Patients undergo single allogeneic UCB transplant on day 0. Patients also undergo irradiated allogeneic PBMC transplant within 8 hours following the UCB infusion.

Drug: cyclophosphamide
Given IV over 1 hour on Day -6; after pre-hydration
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: fludarabine phosphate
Given IV daily over 30 minutes for 5 days (Days -6 to -2)
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: mycophenolate mofetil
Given PO 1.0 g BID Day 1-30
Other Names:
  • Cellcept
  • MMF
Procedure: umbilical cord blood transplantation
Undergo single allogeneic UCB transplant
Other Names:
  • cord blood transplantation
  • transplantation, umbilical cord blood
  • UCB transplantation
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: tacrolimus
Given IV 0.03 mg/kg/d as continuous infusion over 24 hours starting Day -3 with dose adjustments to maintain level of 8-20 mg/ml
Other Names:
  • FK 506
  • Prograf
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo single allogeneic UCB transplant
Procedure: peripheral blood stem cell transplantation
Undergo irradiated allogeneic peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically proven hematologic malignancy with anticipated 2 year survival < 20% with standard therapy; patients age <18 are excluded by virtue of the policies and procedures of the allogeneic hematopoietic stem cell transplant (HSCT) program (Cancer Institute of New Jersey [CINJ]/Robert Wood Johnson University Hospital [RWJUH] is not an approved Pediatric Transplant Center); patients > age 65 are generally not considered candidates for experimental unrelated allogeneic HSCT, as utilized in this study by virtue of the anticipated delayed immune reconstitution, high risk of GVHD, and known negative impact of age on outcomes
  • Patients eligible for this trial will have high risk diseases that include, but are not limited to:

    • Acute myeloid leukemia (AML) in second complete remission (CR2) or greater or early relapse with < 5% marrow blasts and no circulating blasts
    • AML in first complete remission (CR1) with high risk cytogenetics (complex, monosomy 5, monosomy 7, 11q23 (not t(9;11)), t(6;9), chromosome 3, monosomy phenotype and other karyotypes estimated to have =< 20% disease free survival at 3 years) or secondary/transformed AML without favorable cytogenetics;
    • Acute lymphoblastic leukemia (ALL) with t(9;22), 11q23 abnormality or early relapse (< 5% marrow blasts) or CR2 or greater;
    • Chronic myeloid leukemia (CML) resistant/refractory to all commercially available Abelson (abl) kinase inhibitors (e.g. imatinib mesylate, dasatinib, nilotinib) or predicted to be so based upon clinical course or abl kinase domain mutation analysis; or in accelerated phase or blast crisis;
    • High intermediate to high international prognostic score myelodysplasia;
    • Non-Hodgkin lymphoma (NHL)/Hodgkin lymphoma (HL)/other lymphoproliferative diseases resistant/refractory to standard therapies and for whom an autologous transplant is considered to be inappropriate (e.g. bone marrow involvement, chemotherapy refractory disease, prior transplant);
    • Chronic lymphocytic leukemia (CLL) resistant/refractory to standard therapies (e.g. fludarabine) or high risk cytogenetics/fluorescence in situ hybridization (FISH) (e.g. 17p-);
    • Myeloproliferative disorders with progressive disease or cytopenias or clinical symptoms refractory to standard therapy (e.g. hypomethylating agents)
    • Relapsed or refractory multiple myeloma after (or not eligible for) high dose chemotherapy/autologous hematopoietic stem cell rescue and following salvage therapy with thalidomide, lenalidomide or bortezomib/other Food and Drug Administration (FDA)-approved multiple myeloma salvage therapies;
    • Other hematologic malignancies/disorders with anticipated 2 year survival < 20%, as established by available data bases, medical literature and the documented consensus of the Hematologic Malignancies Tumor Study Group
  • Patients must be an allogeneic HSCT candidate but have no standard donor (matched related donor [MRD], human leukocyte antigen [HLA]-matched unrelated donor [MUD] or single UCB unit of appropriate size and HLA type) available
  • Patients must have available UCB unit(s)
  • Patients considered for Arm 2 must not be eligible for Arm 1 and must have an HLA-haploidentical sibling, parent, child, or other relative (uncle, aunt, first cousin, niece or nephew) who meets donor requirements as outlined in Donor Eligibility criteria
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Left ventricular (LV) ejection fraction >= 50%
  • Diffusion capacity of carbon monoxide (DLCO) corrected for hemoglobin > 60%
  • Total bilirubin within normal institutional limits unless the patient has Gilbert's disease
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN)
  • Measured or estimated creatinine clearance > 50 ml/min
  • Hematopoietic stem cell co-morbidity index =< 2
  • There must be a negative pregnancy test for women of childbearing potential within 1 week of therapy; there must be willingness to avoid pregnancy and undergo counseling about contraceptive techniques throughout the course of treatment
  • There must be no uncontrolled infections or active acute or chronic illnesses such as diabetes, angina/myocardial ischemia, cardiac arrhythmia, venous thrombosis/embolism, cerebrovascular disease, seizure disorder, psychiatric illness or other intercurrent illness that is not well controlled or is anticipated to be difficult to control during the proposed therapy
  • The patient must be aware of the high risk and experimental nature of the treatment and provide informed consent
  • The patient must have clearance for HSCT after psychosocial evaluation
  • The patient must have adequate insurance or other support to meet the anticipated financial burden imposed by the costs of therapy
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Relative (parent, child, sibling, first cousin, uncle aunt, nephew, niece) with appropriate HLA match (>= 3/6 HLA A, B, DR match)
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Age >= 18 years old
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Normal hemogram; potential donors not having a normal hemogram may be utilized at the discretion of the Principal Investigator
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Not pregnant or lactating
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C (HCV), Hepatitis B core or human T-lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB Sag)(-); must meet other infectious disease screening criteria utilized by New Brunswick Affiliated Hospital (NBAH) Blood Center
  • DONOR (for allogeneic lymphocytes, Arm 2 only): No uncontrolled infections, other medical or psychological/social conditions, or required medications that might increase the likelihood of patient or donor adverse effects or poor outcomes
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Meet other blood bank criteria for blood product donation (as determined by NBAH Blood Center screening history)
  • DONOR (for allogeneic lymphocytes, Arm 2 only): Donors must be informed of the investigational nature of this study, understand the requirements, potential benefits and potential risks of the experimental treatment, and give written informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

  • Prior extensive radiation therapy that the radiation oncologist feels precludes additional TBI
  • Patients with known human immunodeficiency virus (HIV) are excluded due to side effects of the therapy on the immune system
  • Patients with known active central nervous system (CNS) disease will be excluded from this clinical trial because they often develop progressive neurologic dysfunction unresponsive to HSCT therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01652014

Locations
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Sponsors and Collaborators
University of Medicine and Dentistry New Jersey
Investigators
Principal Investigator: Roger Strair Rutgers Cancer Institute of New Jersey
  More Information

No publications provided

Responsible Party: Rutgers, The State University of New Jersey ( University of Medicine and Dentistry New Jersey )
ClinicalTrials.gov Identifier: NCT01652014     History of Changes
Other Study ID Numbers: 021002, NCI-2011-03187, 0220100266, P30CA072720
Study First Received: July 20, 2012
Last Updated: June 28, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Rutgers, The State University of New Jersey:
Transplantation
Hematopoietic Stem Cell Transplantation

Additional relevant MeSH terms:
Congenital Abnormalities
Blast Crisis
Burkitt Lymphoma
Neoplasms
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Mycoses
Mycosis Fungoides
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on April 14, 2014