Trial Search Results

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

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

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

Stanford University

Collaborator: National Institutes of Health (NIH)

Intervention(s):

  • Procedure: Total Lymphoid Irradiation (TLI)
  • Procedure: Anti-Thymocyte Globulin as Conditioning (ATG)

Phase:

Phase 2

Eligibility


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

Ages Eligible for Study

49 Years - 75 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Physician Referrals
650-723-0822
Not Recruiting