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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00185796
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : March 18, 2015
Sponsor:
Collaborator:
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Robert Lowsky, Stanford University

Tracking Information
First Submitted Date  ICMJE September 12, 2005
First Posted Date  ICMJE September 16, 2005
Last Update Posted Date March 18, 2015
Study Start Date  ICMJE July 2004
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2011)
  • 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 ]
  • 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. [ Time Frame: 7/15/2017 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2011)
  • To evaluate myeloid and platelet engraftment. [ Time Frame: 7/15/2017 ]
  • To evaluate the incidence of acute and chronic GVHD. [ Time Frame: 7/15/2017 ]
  • To evaluate the rate of primary and secondary graft failure. [ Time Frame: 7/15/2017 ]
  • To evaluate the rate of relapse, survival and event-free survival. [ Time Frame: 7/15/2017 ]
  • To evaluate if DLI can be used safely in patients with mixed chimerism. [ Time Frame: 7/15/2017 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TLI & ATG for Non-Myeloablative Allogeneic Transplantation for MDS and MPD
Official Title  ICMJE 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)
Brief Summary To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myeloproliferative Disorders
  • Blood Cancer
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Procedure: Total Lymphoid Irradiation (TLI)
    TLI is administered ten times in 120cGy fractions on day -11 through day -7 and day -4 through day -1
  • Procedure: Anti-Thymocyte Globulin as Conditioning (ATG)
    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 Arms  ICMJE Experimental: TLI/ATG conditioning
Lymphoid irradiation and anti-thymocyte globulin (TLI/ATG).
Interventions:
  • Procedure: Total Lymphoid Irradiation (TLI)
  • Procedure: Anti-Thymocyte Globulin as Conditioning (ATG)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2015)
77
Original Enrollment  ICMJE
 (submitted: September 12, 2005)
14
Actual Study Completion Date  ICMJE February 2015
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.
  • 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.

INCLUSION CRITERIA - RELATED DONORS

  • 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

INCLUSION CRITERIA - UNRELATED DONORS

  • 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.

Exclusion Criteria:GENERAL EXCLUSION CRITERIA

  • 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%.
  • 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.

EXCLUSION CRITERIA - RELATED DONORS

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 49 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00185796
Other Study ID Numbers  ICMJE BMT168
95130
BMT168
13680 ( Other Identifier: Stanford IRB )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert Lowsky, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Robert Lowsky Stanford University
PRS Account Stanford University
Verification Date March 2015

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