Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
Overview
- Phase
- Not Applicable
- Intervention
- fludarabine/busulfan
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- University of Illinois at Chicago
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Number of Participants With Engraftment.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
New conditioning regimens are still needed to maximize efficacy and limit treatment-related deaths of allogeneic transplantation for advanced hematologic malignancies. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.
Detailed Description
Treatment-related mortality and recurrence of disease account for the majority of treatment failures in allogeneic transplantation for advanced hematologic malignancies. The most commonly utilized conditioning regimens consist of cyclophosphamide and total-body irradiation or busulfan and cyclophosphamide. Other agents such as etoposide or thiotepa are sometimes added to maximize the antileukemic effect. New conditioning regimens are however still needed to maximize efficacy and limit treatment-related deaths. Over the past several years, the investigators have evaluated several new conditioning regimens that incorporate fludarabine, a novel immunosuppressant that has limited toxicity and that has synergistic activity with alkylating agents. Recent data have suggested that fludarabine may be used in combination with standard doses of oral or IV busulfan, thus reducing the toxicity previously observed with cyclophosphamide/ busulfan regimens.
Investigators
Damiano Rondelli, MD
Professor
University of Illinois at Chicago
Eligibility Criteria
Inclusion Criteria
- •Patients with the following diseases:
- •Acute myeloid or lymphocytic leukemia in first remission at standard or high-risk for recurrence.
- •Acute leukemia in greater than or equal to second remission, or with early relapse, or partial remission.
- •Chronic myelogenous leukemia in accelerated phase or blast-crisis.
- •Chronic myelogenous leukemia in chronic phase
- •Recurrent or refractory malignant lymphoma or Hodgkin's disease
- •Multiple myeloma.
- •Chronic lymphocytic leukemia, relapsed or with poor prognostic features.
- •Myeloproliferative disorder (polycythemia vera, myelofibrosis) with poor prognostic features.
- •Severe aplastic anemia after failure of immunosuppressive therapy.
Exclusion Criteria
- •Life expectancy is severely limited by concomitant illness.
- •Serum creatinine greater than 1.5 mg/dL or Creatinine Clearance less than 50 ml/min .
- •Serum bilirubin greater than or equal to 2.0 mg/dl, SGPT greater than 3 x upper limit of normal
- •Evidence of chronic active hepatitis or cirrhosis
- •HIV-positive
- •Patient is pregnant
Arms & Interventions
Arm 1
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Intervention: fludarabine/busulfan
Arm 1
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Intervention: ATG
Arm 2
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Intervention: fludarabine/ melphalan
Arm 2
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Intervention: ATG
Outcomes
Primary Outcomes
Number of Participants With Engraftment.
Time Frame: Up to 30 days post-transplant
Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.
Secondary Outcomes
- Participants With 100 Day Transplant-related Mortality.(Up to 100 days post-transplant.)
- Time to ANC and Platelet Engraftment(Up to 30 days post-transplant)
- Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).(Up to 100 days post-transplant (acute GVHD).)