Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

University of Illinois

Status: Completed

Conditions: Myelofibrosis; Acute Leukemia; Polycythemia Vera; Multiple Myeloma; Lymphocytic Leukemia; Malignant Lymphoma; Hodgkin's Disease; Chronic Myelogenous Leukemia; Aplastic Anemia; Acute Myeloid Leukemia; Myeloproliferative Disorder

Treatments: Drug: ATG; Drug: fludarabine/busulfan; Drug: fludarabine/ melphalan

Study type: Interventional

Funder types: Other

Identifiers

NCT01499147

2000-0117

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 patients

Sex: All

Ages: 10 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Arm 1

Active Comparator group

Description:

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

Treatment:

Drug: fludarabine/busulfan

Drug: ATG

Arm 2

Active Comparator group

Description:

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

Treatment:

Drug: fludarabine/ melphalan

Drug: ATG