Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

January 3, 2019 updated by: Case Comprehensive Cancer Center

Umbilical Cord Blood (UCB) Allogeneic Stem Cell Transplant for Hematologic Malignancies

RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant (UCBT) helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from an unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor umbilical cord blood stem cell transplant works in treating patients with hematologic malignancies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

1. To establish the day +180 overall survival after a myeloablative unrelated double unit UCBT in a single institution setting.

SECONDARY OBJECTIVES:

  1. To determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies, who are undergoing myeloablative chemotherapy followed by infusion of double unit UCBT.
  2. To determine the contribution of each umbilical cord unit to immune reconstitution with a focus on both initial (day +21 BM, and +28 PB) and sustained engraftment (day +100 BM; PB at +14, +21, +28, +35, +42, +60, +100, +180, +1 and 2 years).
  3. To determine the probability of overall survival and disease free survival at one and two years.
  4. To describe the incidence of disease recurrence at one and two years in patients post UCBT.
  5. To describe the incidence of acute GVHD and chronic GVHD at 100 days and at one year, respectively.
  6. To determine the incidence of day 100 and 180 treatment related mortality.
  7. To determine the incidence of serious infectious complications in the first year after transplant.
  8. To determine the incidence of donor-derived neutrophil and platelet recovery.
  9. To determine the incidence of secondary lymphoproliferative diseases following transplantation with umbilical cord blood.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1.

TRANSPLANTATION: Patients undergo double-unit umbilical cord blood allogeneic stem cell transplantation on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally every 8 hours on days -3 to 45. After completion of study treatment, patients are followed periodically.

Study Type

Interventional

Enrollment (Actual)

14

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
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

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

12 years to 64 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients will be diagnosed with one of the following hematological malignancies: acute myelogenous leukemia (AML), acute lymphoblastic leukemia, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and myeloproliferative and lymphoproliferative disorders
  • AML--First remission (CR1) with high risk features including a known prior diagnosis of myelodysplasia (MDS); therapy related AML; white cell count at presentation > 100,000; presence of extramedullary leukemia at diagnosis; unfavorable AML subtype (M0, M5-M7); poor cytogenetic markers (abnormalities of chromosome 5, 7 or 8, 11q23, Philadelphia chromosome, complex karyotype)
  • AML--Second remission (CR2) or subsequent remission
  • AML--Relapse/Persistent Disease with < 20% bone marrow blasts
  • ALL--First remission (CR1) at high risk for relapse as defined by: B cell ALL white blood cell count (WBC) at presentation > 30,000 (T cell ALL WBC > 100,000); presence of high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23), t(8;14)
  • ALL--Second remission (CR2) or subsequent remission
  • ALL--Relapse/Persistent Disease with < 20% bone marrow blasts
  • Non-Hodgkin Lymphoma--Induction failure or relapse and sensitive to most recent chemotherapy
  • MDS--Low or Intermediate-1 International Prognostic Scoring System (IPSS) score with: life-threatening cytopenia(s); and/or red cell or platelet transfusion dependence
  • MDS--ANC < 500, recurrent infections, PRBC transfusions > 2 units/month, poor risk cytogenetics, platelet transfusion dependence
  • MDS--Intermediate-2 or High IPSS score
  • CML--Chronic phase I (CP1) and resistant to or intolerant of tyrosine kinase inhibitors (i.e. imatinib, dasatinib, etc.)
  • CML--CP2 or subsequent chronic phase, including chronic phase achieved after induction therapy for blast crisis
  • Myeloproliferative and lymphoproliferative disorders--eligibility to be determined by a consensus of the physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee
  • Myeloproliferative and lymphoproliferative disorders--must have evidence of disease acceleration to be a candidate for umbilical cord blood transplant; myeloproliferative disorders eligible for transplant include chronic myelomonocytic leukemia (CMML) with high IPSS score and myelofibrosis
  • Myeloproliferative and lymphoproliferative disorders--potential lymphoproliferative disorders eligible for transplant include chronic lymphocytic leukemia, prolymphocytic leukemia, and large granular lymphocytic leukemia
  • Good performance status: Karnofsky >= 70 % or ECOG 0-1
  • Calculated creatinine clearance >= 60 mL/min, or measured creatinine clearance >= 60 mL/min (by 24-hour urine collection) if creatinine >= 1.5 or history of renal dysfunction
  • Hepatic Transaminases < 4 x upper limit normal (ULN); total bilirubin < 2.5 mg/dL, unless the patient has a history of benign congenital hyperbilirubinemia (Gilbert's syndrome)
  • Normal cardiac function by echocardiogram or radionuclide scan, (left ventricular ejection fraction > 45%); if the left ventricular ejection fraction is between 40-50%, clearance by an adult cardiologist is required
  • Pulmonary function tests demonstrating FEV1 > 60% of predicted for age
  • Adults must have a DLCOva > 60% normal
  • For patients unable to complete pulmonary function tests clearance by an adult pulmonologist is required
  • Patients will be eligible for the clinical trial under the following conditions: they do NOT have an HLA-A/B/DR B1 identical RELATED bone marrow donor; they do NOT have a 6/6 HLA-identical matched unrelated adult donor; OR a matched related donor transplant is not in the best interest of the patient (i.e., patient's condition precludes waiting on the donor, too much time to prepare the donor, the donor is ineligible due to medical reasons, or in the case of high risk disease a related donor is not appropriated (syngeneic transplant); the decision must be agreed upon by the consensus of physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee; OR their condition precludes waiting to search and find a donor in the National Marrow Donor Registry

Exclusion Criteria:

  • Female patients who are pregnant or breast-feeding
  • HIV or HTLV-1 positivity
  • Any leukemia with a morphologic relapse or persistent disease in the BM with >= 20% blasts (cytogenetic relapse without morphologic evidence of relapse, or cytogenetic persistent disease is acceptable)
  • Active extramedullary leukemia, including CNS disease
  • Prior hematopoietic stem cell transplant (autologous or allogeneic)
  • Uncontrolled infection
  • Patient has an identical related bone marrow donor or a 6/6 HLA-identical matched unrelated donor
  • Any patient who is unable to provide informed consent or comply with the requirements of the protocol

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
PREPARATIVE REGIMEN: Patients receive oral busulfan on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1. TRANSPLANTATION: Patients undergo a double-unit umbilical cord blood allogeneic stem cell transplantation on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally on days -3 to 45.
Other: flow cytometry
Correlative studies
Drug: busulfan
Given orally
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
  • Myelosan
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
  • Enduxan
Drug: methylprednisolone
Given IV
Other Names:
  • A-MethaPred
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: anti-thymocyte globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymphocyte immune globulin
Drug: cyclosporine
Given IV
Other Names:
  • 27-400
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Procedure: bone marrow aspiration
Correlative studies
Procedure: double-unit umbilical cord blood transplantation
Undergo transplantation
Other: cytogenetic analysis
Correlative studies
Other: fluorescence in situ hybridization
Correlative studies
Other Names:
  • fluorescence in situ hybridization (FISH)
Drug: mycophenolate mofetil
Given orally or IV
Other Names:
  • Cellcept
  • MMF
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: On day +180
Number of participants alive at 180 days post engraftment.
On day +180

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematologic Engraftment
Time Frame: On day +42
Number of participants that were able to complete engraftment by day 42.
On day +42
Overall Survival
Time Frame: At 1 year
Number of participants that were alive.
At 1 year
Overall Survival
Time Frame: At 2 years
Number of participants that were alive.
At 2 years
Disease Free
Time Frame: At 1 year
Number of participants that were disease free
At 1 year
Disease Free
Time Frame: At 2 years
Number of participants that were disease free
At 2 years
Recurrence or Relapse
Time Frame: one year in patients post UCBT
Number of subjects that had disease recurrence
one year in patients post UCBT
Recurrence or Relapse
Time Frame: two years post transplant
Number of subjects that had disease recurrence
two years post transplant
Transplant Related Mortality
Time Frame: On day 100 post transplant
Number of subjects that died because of transplant
On day 100 post transplant
Transplant Related Mortality
Time Frame: On day 180 post transplant
Number of subjects that died because of transplant
On day 180 post transplant
Occurrence of Serious Infections
Time Frame: 1 year
Number of participants that had infections
1 year
Immune Reconstitution
Time Frame: Periodically for 2 years
Immunodificency panel to see recovery of immune system. Number of participants that recovered.
Periodically for 2 years
Toxicity Related to UCB Transplantation and Cytoreduction as Assessed by CTC v3.0
Time Frame: by day +42
Number of participants that experienced toxicity related to the transplant
by day +42
Incidence of Acute Graft-versus-host Disease (GVHD)
Time Frame: At 100 days
Number of participants that had acute GVHD
At 100 days
Incidence of Chronic GVHD
Time Frame: At 1 year
Number of participants that have chronic GVHD. Chronic GVHD will be diagnosed and graded on clinical and histological criteria from the Center for International Blood and Marrow Transplant Research (CIBMTR)
At 1 year

Collaborators and Investigators

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

Sponsor

Case Comprehensive Cancer Center

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

September 1, 2007

Primary Completion (ACTUAL)

December 1, 2015

Study Completion (ACTUAL)

December 1, 2015

Study Registration Dates

First Submitted

March 24, 2010

First Submitted That Met QC Criteria

March 25, 2010

First Posted (ESTIMATE)

March 26, 2010

Study Record Updates

Last Update Posted (ACTUAL)

January 23, 2019

Last Update Submitted That Met QC Criteria

January 3, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE3Z07 (OTHER: Case Comprehensive Cancer Center)
  • NCI-2009-01319 (OTHER: NCI/CTRP)

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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