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

July 13, 2016 updated by: University of Medicine and Dentistry of New Jersey

Hematopoietic Stem Cell Transplantation Using Alternate Donor Umbilical Cord Blood Options

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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Cancer Institute Of New Jersey

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Radiation: total-body irradiation
Undergo TBI
Other Names:
  • TBI
Drug: cyclophosphamide
Given IV over 1 hour on Day -6; after pre-hydration
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • 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
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:
  • Prograf
  • FK 506
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo single allogeneic UCB transplant
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.
Radiation: total-body irradiation
Undergo TBI
Other Names:
  • TBI
Drug: cyclophosphamide
Given IV over 1 hour on Day -6; after pre-hydration
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • 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
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:
  • Prograf
  • FK 506
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo single allogeneic UCB transplant
Procedure: umbilical cord blood transplantation
Undergo single allogeneic UCB transplant
Other Names:
  • UCB transplantation
  • cord blood transplantation
  • transplantation, umbilical cord blood
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Engraftment of white blood cells (WBC) (absolute neutrophil count > 500/mm^3)
Time Frame: 3 years
3 years
Non-relapse mortality
Time Frame: 40 months
40 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet engraftment rate (non-transfusion dependent)
Time Frame: At 100 days
At 100 days
Transplant related mortality
Time Frame: At 1 year
At 1 year
Rates of infection requiring hospitalization or prolongation of hospitalization
Time Frame: Up to 2 years
Up to 2 years
Incidence of steroid-refractory acute GVHD
Time Frame: at 100 days
GVHD will be staged per standard guidelines of the American Society for Blood and Bone Marrow Transplantation.
at 100 days
Incidence of extensive chronic GVHD
Time Frame: up to 2 years
GVHD will be staged per standard guidelines of the American Society for Blood and Bone Marrow Transplantation.
up to 2 years
Total time on immunosuppressive therapy
Time Frame: Up to 2 years
Up to 2 years
Time to CD4 count > 200/mm^3
Time Frame: Up to 2 years
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Medicine and Dentistry of New Jersey

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Anticipated)

January 1, 2017

Study Completion (Anticipated)

January 1, 2017

Study Registration Dates

First Submitted

July 20, 2012

First Submitted That Met QC Criteria

July 24, 2012

First Posted (Estimate)

July 27, 2012

Study Record Updates

Last Update Posted (Estimate)

July 14, 2016

Last Update Submitted That Met QC Criteria

July 13, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 021002
  • P30CA072720 (U.S. NIH Grant/Contract)
  • NCI-2011-03187 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 0220100266 (Other Identifier: IRB Number)

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.

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