Treatment of Single or Double Umbilical Cord Trans + Graft-versus-host Disease (GVHD) Prophylaxis w/ Tacrolimus & Mycophenolate Mofetil

May 12, 2014 updated by: Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center

The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-versus-Host Prophylaxis With Tacrolimus and Mycophenolate Mofetil

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant 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 healthy stem 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: To look at the ability of umbilical cord blood cells from one or two unrelated donors to serve as a source of stem cells for people needing a bone marrow transplant.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To determine the safety (as assessed by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord stem cell transplantation in patients with hematological malignancies receiving graft-versus-host disease (GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

Secondary

  • To assess sustained donor engraftment, neutrophil recovery, platelet recovery, incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD, relapse rate, 100-day all-cause mortality, overall survival, and immune reconstitution after single or double umbilical cord stem cell transplantation in patients with hematologic malignancies receiving graft-versus-host disease(GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

OUTLINE:

  • Conditioning: Patients receive myeloablative or reduced-intensity conditioning regimen according to age and prior treatment.

    • Myeloablative conditioning (pediatric patients): Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
    • Myeloablative conditioning (adult patients 18-40 years old): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
    • Reduced-intensity conditioning (patients over 40 and no more than 50 years old OR deemed ineligible for above myeloablative conditioning regimen due to previous treatment): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
  • Umbilical cord blood transplantation (UCBT): All patients undergo single- or double-unit umbilical cord blood transplantation (UCBT)on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -2 to 180 followed by a tapering and mycophenolate mofetil IV or orally twice daily on days 0-100 followed by a tapering over the next 3 months. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0* and continuing until blood counts recover.

NOTE: *In adult patients receiving a reduced intensity transplant, G-CSF will be started when the total white cell count falls below 2.5 x 109/L.

After completion of study treatment, patients are followed monthly for 1 year and then every 2-4 months thereafter.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Not Applicable

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
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
      • Nashville, Tennessee, United States, 37212
        • Veterans Affairs Medical Center - Nashville
      • Nashville, Tennessee, United States, 37067-1631
        • Vanderbilt-Ingram Cancer Center - Cool Springs
      • Nashville, Tennessee, United States, 37067-5615
        • Vanderbilt-Ingram Cancer Center at Franklin

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

No older than 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Patient and UCB Unit Selection:

Inclusion Criteria: General (Adults and Pediatrics)

Only one of the following should be present:

  • Acute leukemia (lymphocytic or myeloid or undifferentiated or biphenotypic) in complete remission 2 or beyond
  • Acute lymphocytic leukemia, Philadelphia chromosome positive in complete remission 1 or beyond
  • Acute myeloid leukemia in complete remission 1 if it has evolved from a myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS).
  • Acute leukemia in complete remission 1 if there is a failure to recover normal blood counts or the development of MDS following induction chemotherapy.
  • Therapy related acute leukemia in complete remission 1 or beyond
  • Chronic myeloid leukemia (CML) chronic phase-1 (imatinib failures, imatinib intolerance), or any CML beyond first chronic phase
  • Myelodysplastic syndromes (Intermediate -1 or higher risk by IPSS)
  • Therapy related MDS (irrespective of IPSS)
  • Multiple myeloma must have had prior chemotherapy or autologous transplant
  • Chronic lymphocytic leukemia must have failed two lines of conventional therapy but still chemosensitive to third line therapy.
  • Chemosensitive Non-Hodgkin's lymphoma or Hodgkin's lymphoma in CR or PR after failing induction therapy.
  • High risk acute leukemia/lymphoma eg Nk/T cell, HTLV associated leukemia/lymphoma, other T cell lymphoma/leukemia in first best response
  • For patients with acute leukemia-they must be in a remission (less than 5% leukemic marrow blasts) at time of study entry.

Inclusion Criteria (Adults - 18 years or older)

  • Karnofsky score of > 70%
  • Estimated creatinine clearance of > 60 ml/min
  • Left ventricular ejection fraction of >50%
  • Pulmonary function test with DLCO, FEV1 and FVC of >60%
  • Total bilirubin and SGOT of < 3.0 x upper limits of normal
  • Note: Age 18- 40 years for adult myeloablative conditioning Age > 40 -50 years for adult reduced intensity conditioning

Inclusion Criteria (Pediatrics - 18 years and younger)

  • Karnofsky or Lansky score of > 70%
  • Estimated Creatinine clearance of > 60 ml/min
  • Left ventricular ejection fraction of >50%
  • Pulmonary function test with FEV1 and FVC of >60% (for patients >6 years of age)
  • Total bilirubin and SGOT of < 3.0 x upper limits of normal
  • Note: All pediatric patients will receive myeloablative conditioning

Inclusion Criteria - Donor Issues

  • No available HLA identical or 1 antigen/allele mismatched (Class I-A, B or Class II DR locus) related donor

Inclusion Criteria: Umbilical Cord Blood Unit-HLA Typing

  • At least a HLA 4/6 match (Class I-A, B by low resolution, Class II-DR by high resolution) to recipient
  • For double UCB SCT each unit should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to recipient, and should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to each other

Inclusion Criteria: Umbilical Cord Blood Unit-Cell dose

  • For Single UCB SCT: the unit will have ≥ 3.5 X 107 NC/kg of recipient body weight (For pediatric patients a cell dose ≥ 3.0 X 107 NC/kg of recipient body weight is acceptable). Recipient body weight will be determined as per standard guidelines.
  • For Double UCB SCT: (done only if no single UCB unit ≥ 3.5 X 107 NC/kg of recipient body weight is available for adults, and ≥ 3.0 X 107 NC/kg of recipient body weight is available for pediatric patients )
  • The larger of the two units (UCB1) will have a minimum cell dose of 2.0 X 107 NC/kg of recipient body weight. The smaller of the two units (UCB2) will have a minimum of 0.5 X 107 NC/kg of recipient body weight.

The total cell dose UCB1 + UCB2 will be ≥ 2.5 X 107 NC/kg of recipient body weight.

-Adult patients eligible for a double UCB SCT but without an appropriate second UCB unit will be enrolled in the study if their single UCB unit contains ≥ 2.5 x 107 NC/kg recipient body weight.

Exclusion Criteria

  • Organ dysfunction as per standard guidelines. Unable to give informed consent (for adults only)
  • Pregnant or lactating
  • Sexually active individuals capable of becoming pregnant or causing a pregnancy who are unable or unwilling to use appropriate contraceptives.
  • Active use of illicit drugs as evidenced by a positive toxicology screen for a substance not prescribed by a medical professional just prior to initiating the preparative regimen
  • Actively smoking as evidenced by a positive nicotine screen just prior to initiating the preparative regimen
  • HIV positive
  • Patients with other unrelated malignancies will be excluded except:
  • diagnosis of skin cancer (squamous cell or basal cell)
  • diagnosis of cervical dysplasia (CIN I-III)
  • any other malignancy which is currently in remission and was treated with curative intent more than 5 years preceding study entry
  • In patients with secondary MDS or secondary acute leukemias-the previous non-hematopoietic neoplasm should be in remission but can be within 5 years of study entry

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: Pediatric Myeloablative conditioning
Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxin
Drug: methylprednisolone
Given IV
Other Names:
  • Medrol
Biological: anti-thymocyte globulin
Given IV
Other Names:
  • ATG
Radiation: total-body irradiation
Given daily for 1-4 days
Experimental: Adult Myeloablative conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
Drug: fludarabine phosphate
Given IV
Other Names:
  • Fludara
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxin
Radiation: total-body irradiation
Given daily for 1-4 days
Experimental: Reduced-intensity conditioning
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
Drug: fludarabine phosphate
Given IV
Other Names:
  • Fludara
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxin
Radiation: total-body irradiation
Given daily for 1-4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With 100-day Non-relapse Mortality
Time Frame: 100 days
Evaluate the safety (as determined by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord blood (UCB)stem cell transplant (SCT) in adult or pediatric patients with hematologic malignancies receiving graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil (MMF).
100 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Sustained Donor Engraftment of Umbilical Cord Blood Stem Cells
Time Frame: 42 days
Recovery of the neutrophil portion of white blood cells and showing complete donor cells.
42 days
Number of Participants With Acute Graft-versus-host Disease (GVHD)
Time Frame: 100 days
Participants who exhibit acute GVHD.
100 days
Number of Participants Who Relapsed at 1 Year
Time Frame: 1 year
1 year
Number of Subjects With All-cause Mortality
Time Frame: at 100 days
Death from any cause at 100 days
at 100 days
Overall Survival
Time Frame: 1 year
Overall survival at 1 year
1 year
Number of Participants With Chronic Graft Versus Host Disease (GVHD)
Time Frame: 100 days
As opposed to acute GVHD, which is characterized by rash, cholestasis, and enteritis, chronic GVHD is characterized by nausea, anorexia, ocular and oral sicca, and other organ involvement
100 days

Collaborators and Investigators

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

Sponsor

Vanderbilt-Ingram Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Brian Engelhardt, MD, Vanderbilt-Ingram 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, 2005

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

January 31, 2008

First Submitted That Met QC Criteria

January 31, 2008

First Posted (Estimate)

February 6, 2008

Study Record Updates

Last Update Posted (Estimate)

May 20, 2014

Last Update Submitted That Met QC Criteria

May 12, 2014

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VICC BMT 0552
  • VU-VICC-BMT-0552

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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