Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

NCT ID: NCT01499147

Last Updated: 2018-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2013-05-31

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

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

Group Type: ACTIVE_COMPARATOR

fludarabine/busulfan

Intervention Type: 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.

ATG

Intervention Type: DRUG

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

Arm 2

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

Group Type: ACTIVE_COMPARATOR

fludarabine/ melphalan

Intervention Type: 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).

ATG

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

ATG

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

Intervention Type: DRUG

Other Intervention Names

Fludarabine: Fludarabine Phosphate; Fludara; Busulfan: Busulfex; Myleran; Fludarabine: Fludarabine phosphate; Fludara; Melphalan: Alkeran; Thymoglobulin

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Damiano Rondelli, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Damiano Rondelli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

2000-0117

Identifier Type: -

Identifier Source: org_study_id