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Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Damiano Rondelli, MD, University of Illinois at Chicago
ClinicalTrials.gov Identifier:
NCT01499147
First received: November 23, 2011
Last updated: May 17, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention
Acute Myeloid Leukemia Acute Leukemia Chronic Myelogenous Leukemia Malignant Lymphoma Hodgkin's Disease Multiple Myeloma Lymphocytic Leukemia Myeloproliferative Disorder Polycythemia Vera Myelofibrosis Aplastic Anemia Drug: fludarabine/busulfan Drug: fludarabine/ melphalan Drug: ATG

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Damiano Rondelli, MD, University of Illinois at Chicago:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • Participants With 100 Day Transplant-related Mortality. [ Time Frame: Up to 100 days post-transplant. ]
    Day 100 transplant-related mortality was measured in both groups.

  • Time to ANC and Platelet Engraftment [ Time Frame: Up to 30 days post-transplant ]
    Days

  • Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD). [ Time Frame: Up to 100 days post-transplant (acute GVHD). ]
    Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.


Enrollment: 100
Study Start Date: February 2000
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Drug: fludarabine/busulfan
All patients below age 55, should receive fludarabine/busulfan, and ATG in case of unrelated or mismatched donor, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl) and/or specific medical conditions such as preventing a standard myeloablative treatment, as per discussion with the PI.
Other Names:
  • Fludarabine:
  • Fludarabine Phosphate
  • Fludara
  • Busulfan:
  • Busulfex
  • Myleran
Drug: ATG
Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.
Other Name: Thymoglobulin
Active Comparator: Arm 2
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Drug: fludarabine/ melphalan
All patients above age 55 or below age 65, should receive fludarabine/melphalan, and ATG, unless there is significant pulmonary, hepatic or cardiac damage: (E.g FEV1 <40%, DLCO<50%, LVEF<40, Serum bilirubin >1.5 mg% or serum transaminases > 2x nl).
Other Names:
  • Fludarabine:
  • Fludarabine phosphate
  • Fludara
  • Melphalan:
  • Alkeran
Drug: ATG
Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.
Other Name: Thymoglobulin

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.
  Eligibility

Ages Eligible for Study:   10 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • Age 10-65 years.
  • Zubrod performance status less than or equal to 2.
  • Adequate cardiac and pulmonary function. Patients with decreased LVEF < 40% or DLCO < 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol.
  • Patient or guardian able to sign informed consent.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01499147

Locations
United States, Illinois
University of Illinois at Chicago Medical Center
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Damiano Rondelli, MD University of Illinois at Chicago
  More Information

Responsible Party: Damiano Rondelli, MD, Professor, University of Illinois at Chicago
ClinicalTrials.gov Identifier: NCT01499147     History of Changes
Other Study ID Numbers: 2000-0117
Study First Received: November 23, 2011
Results First Received: June 19, 2015
Last Updated: May 17, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Damiano Rondelli, MD, University of Illinois at Chicago:
Acute myeloid leukemia
First remission
Acute lymphocytic leukemia
Acute leukemia
Second remission
Early relapse
Partial remission
Accelerated phase
Blast-crisis
Chronic myelogenous leukemia
Chronic phase
Recurrent malignant lymphoma
Refractory malignant lymphoma
Hodgkin's disease
Multiple myeloma.
Chronic lymphocytic leukemia
Myeloproliferative disorder
Polycythemia vera
Myelofibrosis
Severe aplastic anemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Primary Myelofibrosis
Anemia, Aplastic
Hodgkin Disease
Polycythemia
Polycythemia Vera
Myeloproliferative Disorders
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Bone Marrow Diseases
Anemia
Fludarabine

ClinicalTrials.gov processed this record on August 18, 2017