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Completed

NCT Number: NCT01499147

Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

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.

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Key information

Conditions

Acute Myeloid Leukemia Acute Leukemia Anemia Anemia, Aplastic Aplastic Anemia Blast Crisis Blood Protein Disorders Bone Marrow Diseases Bone Marrow Failure Disorders Bone Marrow Neoplasms Carcinogenesis Cardiovascular Diseases Cell Transformation, Neoplastic Chronic Disease Chronic Myelogenous Leukemia Disease Attributes Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hodgkin Disease Hodgkin's Disease Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Acute Lymphatic Diseases Lymphocytic Leukemia Lymphoma Lymphoproliferative Disorders Malignant Lymphoma Multiple Myeloma Myelofibrosis Myeloproliferative Disorder Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Neoplastic Processes Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Polycythemia Vera Precursor Cell Lymphoblastic Leukemia-Lymphoma Primary Myelofibrosis Recurrence Vascular Diseases

Age range

10 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

fludarabine/busulfan

Drug

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

fludarabine/ melphalan

Drug

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

ATG

Drug

Patients receiving a transplant from a matched unrelated or mismatched related/unrelated donor would receive ATG in the conditioning regimen.

Other names: Thymoglobulin

Primary outcomes

  1. 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

  1. 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.

  2. Time to ANC and Platelet Engraftment

    Time frame: Up to 30 days post-transplant

    Days to ANC or platelet engraftment

  3. 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.

Sponsors and collaborators

Lead sponsor

University of Illinois at Chicago

Other

Registry information

Important dates

Study start
2000
Primary completion
2013
Study completion
2013
First posted
Dec 26, 2011
Registry last updated
Nov 8, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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