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URL http://www.rockymountainbmt.com/clinical_trials/1992---A-Multi-center-Phase-III-Study-Comparing-Myeloablative-to-Nonmyeloablative-Transplant-Conditioning-in-Patients-with-Myelodysplastic-Syndrome-or-Acute-Myelogenous-Leukemia-52.html

1992 - A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients with Myelodysplastic Syndrome or Acute Myelogenous Leukemia

Principal Investigator: Peter A. McSweeney, MD

Protocol Number: RMBMT 159


Major Objectives

Determine whether the conditioning intensity affects outcomes after HCT in patients with MDS or AML who have <5% marrow myeloblasts at the time of HCT.

Patient Selection

Inclusion Criteria:

  1. MDS or tAML (transformed from MDS)
  2. De novo AML beyond first remission
  3. Intermediate or high risk de novo AML in first complete response-(unrelated donor recipients only)
  4. Chemotherapy required prior to HCT for all patients
    1. Interval between start of a cycle of chemotherapy and infusion of donor stem cells must be at least 30 days.
    2. All patients must have <5% myeloblasts based on marrow morphology performed within 21 days prior to start of conditioning regimen and at least 28 days after start of pre-transplant chemotherapy
    3. All patients must have no circulating peripheral blood myeloblasts present based on morphologic analysis
  5. Age ≤65 years for patients with related donors
  6. Age ≤60 years for patients with unrelated donors
  7. HCT-Specific Comorbidity Index Score (HCT-CI) <3

Exclusion Criteria:

  • ≥5% marrow myeloblasts by morphology at time of HCT.
  • HIV seropositivity
  • Fungal infections with radiographic progression after appropriate therapy for greater than one month.
  • Organ dysfunction
    1. Symptomatic coronary artery disease or ejection fraction <35%.
    2. DLCO <65%, FEV1 <65% or receiving supplementary continuous oxygen.
    3. Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension. Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, 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 will be excluded.
  • Karnofsky Performance Score <70
  • Lansky-Play Performance Score <70 for pediatric patients.
  • Life expectancy severely limited (<1 year) by diseases other than malignancy.
  • Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment.
  • Patients with active non-hematological malignancies except:
    1. Patients with follicular or low grade lymphoma will be eligible as long as they have not and do not require active treatment for control of their disease
    2. Patients with localized non-melanoma skin malignancies
  • Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication.
  • Females who are pregnant or breastfeeding.
  • Patients with systemic, uncontrolled infections.
  • Active CNS disease as identified by positive CSF cytospin.

Donor Selection

Inclusion Criteria:

  1. Related or unrelated donors who are genotypically or phenotypically matched by high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1). Class 1 single allele mismatch allowed.
  2. Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0201, and this type of mismatch is not allowed.
  3. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion.
  4. Age ≥12 years.
  5. Donors must consent to PBSC mobilization with G-CSF and leukaphereses. Bone marrow as a source of stem cells will not be allowed.
  6. Donor must have adequate veins for leukaphereses or agree to placement of central venous catheter (femoral, subclavian).

Exclusion Criteria:

  1. Identical twin.
  2. Age < 12 years.
  3. Pregnancy.
  4. HIV seropositivity.
  5. Inability to achieve adequate venous access.
  6. Known adverse reaction to G-CSF.