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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

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

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

NCT ID

NCT01499147

First Posted

November 23, 2011

Last Updated

October 9, 2018

Sponsor

University of Illinois at Chicago

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

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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