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Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Primary Purpose

Acute Myeloid Leukemia, Acute Leukemia, Chronic Myelogenous Leukemia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
fludarabine/busulfan
fludarabine/ melphalan
ATG
Sponsored by
University of Illinois at Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring 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

Eligibility Criteria

10 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Illinois at Chicago Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Arm 1

Arm 2

Arm Description

All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.

All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.

Outcomes

Primary Outcome Measures

Number of Participants With Engraftment.
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.
Day 100 transplant-related mortality was measured in both groups.
Time to ANC and Platelet Engraftment
Days to ANC or platelet engraftment
Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).
Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.

Full Information

First Posted
November 23, 2011
Last Updated
October 9, 2018
Sponsor
University of Illinois at Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT01499147
Brief Title
Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
Official Title
Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Illinois at Chicago

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Leukemia, Chronic Myelogenous Leukemia, Malignant Lymphoma, Hodgkin's Disease, Multiple Myeloma, Lymphocytic Leukemia, Myeloproliferative Disorder, Polycythemia Vera, Myelofibrosis, Aplastic Anemia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Active Comparator
Arm Description
All patients below age 55 should receive fludarabine/busulfan and ATG in case of unrelated or mismatched donor.
Arm Title
Arm 2
Arm Type
Active Comparator
Arm Description
All patients above age 55 or below age 65 should receive fludarabine/ melphalan and ATG.
Intervention Type
Drug
Intervention Name(s)
fludarabine/busulfan
Other Intervention Name(s)
Fludarabine:, Fludarabine Phosphate, Fludara, Busulfan:, Busulfex, Myleran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine/ melphalan
Other Intervention Name(s)
Fludarabine:, Fludarabine phosphate, Fludara, Melphalan:, Alkeran
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
ATG
Other Intervention Name(s)
Thymoglobulin
Intervention Description
Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.
Primary Outcome Measure Information:
Title
Number of Participants With Engraftment.
Description
Median time to ANC engraftment and platelet engraftment in both groups as well as the transfusion requirements measured within 30 days after transplant.
Time Frame
Up to 30 days post-transplant
Secondary Outcome Measure Information:
Title
Participants With 100 Day Transplant-related Mortality.
Description
Day 100 transplant-related mortality was measured in both groups.
Time Frame
Up to 100 days post-transplant.
Title
Time to ANC and Platelet Engraftment
Description
Days to ANC or platelet engraftment
Time Frame
Up to 30 days post-transplant
Title
Number of Participants With Moderate to Severe (Grade 2-4) Acute Graft Versus Host Disease (GVHD).
Description
Acute GVHD grade 2-4 was assessed in patients in the FluBU and FluMel groups up to 100 days after transplant.
Time Frame
Up to 100 days post-transplant (acute GVHD).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damiano Rondelli, MD
Organizational Affiliation
University of Illinois at Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Illinois at Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes

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Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

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