Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Multiple Myeloma Clinical Trial

Official title:

Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01499147
• Other study ID #: 2000-0117
• Status: Completed
• Phase: N/A
• Start date: February 2000
• Est. completion date: May 2013

Study information

• Verified date: October 2018
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia
• Acute Myeloid Leukemia
• Anemia, Aplastic
• Aplastic Anemia
• Chronic Myelogenous Leukemia
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphocytic Leukemia
• Lymphoma
• Malignant Lymphoma
• Multiple Myeloma
• Myelofibrosis
• Myeloproliferative Disorder
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis

Intervention

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

Locations

Country	Name	City	State
United States	University of Illinois at Chicago Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 30 days post-transplant
Secondary	Participants With 100 Day Transplant-related Mortality.	Day 100 transplant-related mortality was measured in both groups.	Up to 100 days post-transplant.
Secondary	Time to ANC and Platelet Engraftment	Days to ANC or platelet engraftment	Up to 30 days post-transplant
Secondary	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.	Up to 100 days post-transplant (acute GVHD).