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

This study has been terminated.
(slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00608517
First received: January 31, 2008
Last updated: May 12, 2014
Last verified: May 2012

January 31, 2008
May 12, 2014
September 2005
March 2008   (final data collection date for primary outcome measure)
Number of Participants With 100-day Non-relapse Mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
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).
Non-relapse mortality at 100 days [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00608517 on ClinicalTrials.gov Archive Site
  • Number of Participants With Sustained Donor Engraftment of Umbilical Cord Blood Stem Cells [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Recovery of the neutrophil portion of white blood cells and showing complete donor cells.
  • Number of Participants With Acute Graft-versus-host Disease (GVHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Participants who exhibit acute GVHD.
  • Number of Participants Who Relapsed at 1 Year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Number of Subjects With All-cause Mortality [ Time Frame: at 100 days ] [ Designated as safety issue: Yes ]
    Death from any cause at 100 days
  • Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Overall survival at 1 year
  • Number of Participants With Chronic Graft Versus Host Disease (GVHD) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    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
  • Sustained donor engraftment [ Designated as safety issue: No ]
  • Neutrophil and platelet recovery [ Designated as safety issue: Yes ]
  • Incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD [ Designated as safety issue: Yes ]
  • Relapse rate [ Designated as safety issue: No ]
  • All-cause mortality at 100 days [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Treatment of Single or Double Umbilical Cord Trans + Graft-versus-host Disease (GVHD) Prophylaxis w/ Tacrolimus & Mycophenolate Mofetil
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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Biological: anti-thymocyte globulin
    Given IV
    Other Name: ATG
  • Drug: cyclophosphamide
    Given IV
    Other Name: Cytoxin
  • Drug: fludarabine phosphate
    Given IV
    Other Name: Fludara
  • Drug: methylprednisolone
    Given IV
    Other Name: Medrol
  • Radiation: total-body irradiation
    Given daily for 1-4 days
    Other Name: total-body irradiation
  • 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.
    Interventions:
    • Biological: anti-thymocyte globulin
    • Drug: cyclophosphamide
    • Drug: methylprednisolone
    • Radiation: total-body irradiation
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
    • Radiation: total-body irradiation
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
    • Radiation: total-body irradiation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
May 2011
March 2008   (final data collection date for primary outcome measure)

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
Both
up to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00608517
VICC BMT 0552, VU-VICC-BMT-0552
Yes
Brian Engelhardt, MD, Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Study Chair: Brian Engelhardt, MD Vanderbilt-Ingram Cancer Center
Vanderbilt-Ingram Cancer Center
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP