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Graft Versus Host DiseaseNCT00608517

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

A study testing anti-thymocyte globulin, cyclophosphamide and fludarabine phosphate in people with Graft Versus Host Disease and Leukemia, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 50 years
Conditions the study is for
Graft Versus Host Disease, Leukemia, Lymphoma
What is being tested?
anti-thymocyte globulin, cyclophosphamide and fludarabine phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
4 sitesUnited States
Study dates
Sep 2005to May 2011
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites
  • Vanderbilt-Ingram Cancer Center - Cool Springs

    Nashville, Tennessee, 37067-1631

  • Vanderbilt-Ingram Cancer Center at Franklin

    Nashville, Tennessee, 37067-5615

  • Veterans Affairs Medical Center - Nashville

    Nashville, Tennessee, 37212

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

Other trials in United States

About this study

Official title: 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.

Read the 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.

Keywords
graft versus host disease, accelerated phase chronic myelogenous leukemia, 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), blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, de novo myelodysplastic syndromes, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, myelodysplastic/myeloproliferative disease, unclassifiable, nodal marginal zone B-cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma
Medical subject headings
Graft vs Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00608517
Study groupRoleWhat they receive
Pediatric Myeloablative conditioningExperimentalPatients 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.
Receives: Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: methylprednisolone; Radiation: total-body irradiation
Adult Myeloablative conditioningExperimentalPatients 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.
Receives: Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: total-body irradiation
Reduced-intensity conditioningExperimentalPatients 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.
Receives: Drug: cyclophosphamide; Drug: fludarabine phosphate; Radiation: total-body irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With 100-day Non-relapse Mortality

    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).

    Measured: 100 days

Secondary outcomes (6)
  1. Number of Participants With Sustained Donor Engraftment of Umbilical Cord Blood Stem Cells

    Recovery of the neutrophil portion of white blood cells and showing complete donor cells.

    Measured: 42 days

  2. Number of Participants With Acute Graft-versus-host Disease (GVHD)

    Participants who exhibit acute GVHD.

    Measured: 100 days

  3. Number of Participants Who Relapsed at 1 Year

    Measured: 1 year

  4. Number of Subjects With All-cause Mortality

    Death from any cause at 100 days

    Measured: at 100 days

  5. Overall Survival

    Overall survival at 1 year

    Measured: 1 year

  6. Number of Participants With Chronic Graft Versus Host Disease (GVHD)

    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

    Measured: 100 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2008 (estimated)
  2. Study startSep 2005
  3. Primary completionMar 2008
  4. Study completionMay 2011

Why it stopped: slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00608517
Sponsor's protocol ID
VICC BMT 0552
Other IDs
VU-VICC-BMT-0552
Status last verified
May 2012
First submitted
31 Jan 2008
Last updated
20 May 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A study testing anti-thymocyte globulin, cyclophosphamide and fludarabine phosphate in people with Graft Versus Host Disease and Leukemia, run by Vanderbilt-Ingram Cancer Center at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 100-day Non-relapse Mortality (time frame: 100 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2014.

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