MDS and AML are predominantly diseases of older patients. For patients with advanced or chemotherapy refractory disease HCT is currently the only strategy that offers curative therapy. Unfortunately, this modality is available only to a small proportion of patients.
Conditions
Interventions
Trade Name: Fludara
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Fludarabin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Trade
Sponsors
University of Technology Dresden
Eligibility
Sex/Gender
All
Inclusion criteria
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 a. Interval between start of a cycle of chemotherapy and infusion of donor stem cells must be at least 30 days. b. All patients must have =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Greater than or equal to 5% marrow myeloblasts by morphology at time of HCT. 2. HIV seropositivity 3. Fungal infections with radiographic progression after appropriate therapy for greater than one month. 4. Organ dysfunction a. Symptomatic coronary artery disease or ejection fraction 3 mg/dL, and symptomatic biliary disease will be excluded. 5. Karnofsky Performance Score <70 (Appendix F). 6. Lansky-Play Performance Score <70 (Appendix G) for pediatric patients. 7. Life expectancy severely limited (<1 year) by diseases other than malignancy. 8. Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment. 9. Patients with active non-hematological malignancies except: a. 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 b. Patients with localized non-melanoma skin malignancies 10. Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication. 11. Patients with systemic, uncontrolled infections. 12. Active CNS disease as identified by positive CSF cytospin. 13. Known or current abuse of drugs, medications or alcohol 14. Subjects unlikely to comply with the requirements of the protocol 15. Pregnancy or lactation 16. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy or are using a highly effective method of birth control (defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner 17. Participation in another clinical trial within the last four weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 1. Progression-free survival 2. NRM at day +100 and at 1 year 3. Donor cell engraftment 4. Incidence of disease progression/relapse 5. Interdose variability and evaluation of a limited sampling strategy with IV Bu 6. Incidence and severity of acute and chronic GvHD 7. Number of days hospitalized 8. Number of transfusions post-transplant ;Primary end point(s): Two year overall survival | — |
Countries
Germany
Outcome results
None listed