Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies - Full Text View

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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: 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 University of Illinois:

Primary Outcome Measures:

To determine the rate of engraftment. [ Time Frame: Up to 30 days post-transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the rate of moderate to severe (grade 2-4) acute and chronic graft versus host disease (GVHD). [ Time Frame: Up to 100 days post-transplant (acute GVHD). ] [ Designated as safety issue: Yes ]
To determine the 100 day transplant-related mortality. [ Time Frame: Up to 100 days post-transplant. ] [ Designated as safety issue: Yes ]
To determine the rate of engraftment. [ Time Frame: Up to 90 days post-transplant ] [ Designated as safety issue: Yes ]
To determine the rate of moderate to severe (grade 2-4) acute and chronic graft versus host disease (GVHD). [ Time Frame: Up to two years post-transplant (chronic GVHD). ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	184
Study Start Date:	February 2000
Estimated Study Completion Date:	February 2015
Estimated Primary Completion Date:	February 2014 (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
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

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

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

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
Genders Eligible for Study:	Both
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

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

Investigators

Principal Investigator:

Damiano Rondelli, MD

University of Illinois

More Information

No publications provided

Responsible Party:	Damiano Rondelli, MD, Professor, University of Illinois
ClinicalTrials.gov Identifier:	NCT01499147 History of Changes
Other Study ID Numbers:	2000-0117
Study First Received:	November 23, 2011
Last Updated:	January 17, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Illinois:

Acute myeloid leukemia
First remission
Acute lymphocytic leukemia
Acute leukemia
Second remission
Early relapse
Partial remission
Chronic myelogenous leukemia
Accelerated phase
Blast-crisis

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:

Primary Myelofibrosis
Anemia
Anemia, Aplastic
Neoplasms
Hodgkin Disease
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myeloproliferative Disorders
Polycythemia

Polycythemia Vera
Acute Disease
Hematologic Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders

ClinicalTrials.gov processed this record on May 16, 2013