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Myeloproliferative DisordersPhase 2NCT00185796

TLI & ATG for Non-Myeloablative Allogeneic Transplantation for MDS and MPD

A Phase 2 study testing Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin as Conditioning (ATG) in people with Myeloproliferative Disorders and Blood Cancer, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD. Read more about this study

Who is it for?
Ages 49 to 75 years
What is being tested?
Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin as Conditioning (ATG)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
1 siteUnited States
Study dates
Jul 2004to Feb 2015
Phase
Phase 2
Are there results?
None posted in the registry

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 49 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • GENERAL INCLUSION CRITERIA
  • General inclusion criteria must include at least one of the following:
  • Patients aged > 49 and < 75 years with MDS or MPD
  • Patients aged < 49 years at high risk for regimen related toxicity using standard high dose regimens. Factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart.
  • Patients with secondary MDS following a prior autologous transplant.
  • An HLA-identical related or an HLA-matched unrelated donor is available. ABO incompatibility is acceptable.
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  • A signed informed consent form.
  • MYELODYSPLASTIC SYNDROME CRITERIA
  • Diagnosis of MDS classifiable by the FAB system as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), refractory anemia with excess blasts (RAEB), and MDS transformed to acute leukemia.
  • Patients with advanced MDS must be cytoreduced to < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. The cytoreductive regimen will be determined by referring centers.
  • Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.
  • All patients with high risk disease, for example "intermediate-2" or "high risk" disease by the IPSS score. Other selected patients with a lower IPSS score may be considered but only after discussion with the BMT attending physicians, as a group, and the PI of the study.
  • MYELOPROLIFERATIVE DISORDERS
  • Myeloproliferative disorders to be included:
  • Philadelphia chromosome-negative CML.
  • Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to post-polycythemic marrow fibrosis.
  • Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis.
  • Patients with agnogenic myeloid metaplasia with high risk disease, for example "intermediate" or "high risk" according to the Lille Scoring System.
  • Patients must be cytoreduced to < 10% marrow blasts. Less than 10% marrow blasts must be documented by marrow examination within 1 month of initiation of TLI/ATG. The cytoreductive regimen will be determined by referring centers.
  • Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.
  • Related to the patient and is genotypically or phenotypically HLA-identical.
  • Donor age < 75 unless cleared by P.I
  • Capable of giving written, informed consent.
  • Donor must consent to PBSC mobilization with G-CSF and apheresis
  • Donors must be HLA-matched as defined by the following criteria:
  • Matched for HLA-DRB1 and DQB1 by high resolution typing.
  • Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens, and molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens by high resolution typing.
  • Donor must consent to PBSC mobilization with G-CSF and apheresis. Bone marrow unrelated donors are not eligible for this protocol.

Who cannot join

  • Organ dysfunction as defined by the following:
  • Renal: Patients with a normal creatinine are eligible for study without the need for a 24 hr urine collection for creatinine clearance. Patients with an elevated creatinine require a 24 hr urine collection. If the creatinine clearance is < 50 ml/min patients will be determined for inclusion on a case by case basis.
  • Cardiac: Ejection fraction < 40%, symptomatic congestive heart failure requiring therapy, poorly controlled cardiac arrythmias, or poorly controlled hypertension with inability to maintain a steady-state blood pressure of 150/90.
  • Pulmonary: Requirement for supplemental oxygen administration, or pulmonary function testing showing (1) DLCO < 50% of predicted, (2) TLC < 30%, or (3) FEV1 < 30%.
  • Hepatic: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function and degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis if the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess. Biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, and symptomatic biliary disease.
  • Bone marrow documenting blast count >=10%.
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  • Presence of active of non-hematologic malignancy (except localized non-melanoma skin malignancies) or hematologic malignancy other than MDS or MPD as listed in inclusion criteria.
  • Active CNS involvement of disease.
  • Karnofsky performance score <= 60% or Lansky-Play Performance score <50 for pediatric patients.
  • Life expectancy severely limited by diseases other than malignancy.
  • Fungal infections with radiological progression despite with an amphotericin product or active triazole for > 1 month.
  • Active bacterial infection.
  • Patients of fertile age who refuse contraception for a twelve month period post-transplant.
  • Pregnant or lactating females.
  • HIV seropositivity.
  • Severe psychological illness.
  • Identical twin
  • Any contra-indication to the administration of subcutaneous G-CSF at a dose of 16mg/kg/d for five consecutive days
  • Serious medical or psychological illness
  • Pregnant or lactating females
  • Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
  • HIV seropositivity

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (Except CML)

To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.

Read the detailed description

Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (except CML). To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.

Being tested
Total Lymphoid Irradiation (TLI), Anti-Thymocyte Globulin as Conditioning (ATG)
Medical subject headings
Myeloproliferative Disorders, Hematologic Neoplasms, Myelodysplastic Syndromes

What participants receive

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

  • Total Lymphoid Irradiation (TLI)Procedure or surgery

    TLI is administered ten times in 120cGy fractions on day -11 through day -7 and day -4 through day -1

  • Anti-Thymocyte Globulin as Conditioning (ATG)Procedure or surgery

    Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. Thymoglobulin doses will be based on the adjusted ideal body weight if the patient is greater than or equal to 15 kg over ideal body weight.

Study groups in NCT00185796
Study groupRoleWhat they receive
TLI/ATG conditioningExperimentalLymphoid irradiation and anti-thymocyte globulin (TLI/ATG).
Receives: Procedure: Total Lymphoid Irradiation (TLI); Procedure: Anti-Thymocyte Globulin as Conditioning (ATG)

What is being measured

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

  1. To improve survival outcome for selected patients with advanced stages of MDS and MPD with non-myeloablative allogeneic HCT from related and unrelated donors.

    Measured: 7/15/2017

  2. To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.

    Measured: 7/15/2017

Secondary outcomes (5)

  1. To evaluate myeloid and platelet engraftment.

    Measured: 7/15/2017

  2. To evaluate the incidence of acute and chronic GVHD.

    Measured: 7/15/2017

  3. To evaluate the rate of primary and secondary graft failure.

    Measured: 7/15/2017

  4. To evaluate the rate of relapse, survival and event-free survival.

    Measured: 7/15/2017

  5. To evaluate if DLI can be used safely in patients with mixed chimerism.

    Measured: 7/15/2017

Timeline

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

  1. First posted16 Sep 2005 (estimated)
  2. Study startJul 2004
  3. Primary completionApr 2014
  4. Study completionFeb 2015

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00185796
Sponsor's protocol ID
BMT168
Other IDs
95130, BMT168, NCT00185796, 13680
Status last verified
Mar 2015
First submitted
12 Sep 2005
Last updated
18 Mar 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin as Conditioning (ATG) in people with Myeloproliferative Disorders and Blood Cancer, run by Stanford University at 1 site 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 28 inclusion and 22 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: finished, as of the sponsor's last update on 18 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To improve survival outcome for selected patients with advanced stages of MDS and MPD with non-myeloablative allogeneic HCT from related and unrelated donors. (time frame: 7/15/2017). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00185796.

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 18 Mar 2015.

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