Busulfan and Fludarabine Before Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00301912
• Other study ID #: CDR0000463168
• Secondary ID: UCSF-02257UCSF-2
• Status: Withdrawn
• Phase: Phase 2
• First received: March 9, 2006
• Last updated: October 1, 2012
• Start date: January 2002

Study information

• Verified date: October 2012
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more cancer cells are killed. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Tacrolimus and methotrexate may stop this from happening.

PURPOSE: This phase II trial is studying how well giving busulfan together with fludarabine before donor stem cell transplant works in treating patients with hematologic cancer.

Description:

OBJECTIVES:

Primary

• Determine the safety, in terms of treatment-related mortality at 100 days post-transplantation, of a myeloablative preparative regimen comprising busulfan and fludarabine and graft-vs-host disease (GVHD) prophylaxis comprising tacrolimus and methotrexate in patients with hematopoietic disorders undergoing matched unrelated donor stem cell transplantation.

• Determine the efficacy, in terms of overall survival at 1-year post-transplantation, in patients treated with this regimen.

Secondary

• Determine organ toxicity in patients treated with this regimen.

• Determine neutrophil and platelet recovery in patients treated with this regimen.

• Determine the incidence and severity of acute and chronic GVHD in patients treated with this regimen.

OUTLINE:

• Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and fludarabine IV over 30 minutes on days -7 to -3.

• Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.

• Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -2 and continuing until discharged from the hospital (may convert to oral dosing administered twice daily when tolerated) and methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematopoietic disorders:

• Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

• Chronic phase disease failing imatinib mesylate therapy

• Progressive disease OR failed to achieve a major cytogenetic response at 1 year after initiation of therapy

• Accelerated phase disease, meeting 1 of the following criteria:

• Failed to achieve complete cytogenetic remission at 1 year after initiation of therapy

• Failed to achieve any cytogenetic response at 3 or 6 months during therapy

• Progressive disease, demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks

• Blast crisis with < 10% blasts in bone marrow within 6 weeks of transplantation

• Acute myeloid leukemia (AML), meeting 1 of the following criteria:

• In second or greater remission

• In first remission with poor prognosis cytogenetics [-5, -5q, -7, -7q and = 2 cytogenetic abnormalities, t(6,9), t(9,11), or Philadelphia chromosome]

• In hematologic remission but with persistent cytogenetic abnormalities

• Primary refractory AML with < 10% blasts in bone marrow within 6 weeks of transplantation

• Myelodysplasia with < 20% blasts in bone marrow within 6 weeks of transplantation and meeting 1 of the following criteria:

• Advanced disease (International Prognostic Scoring System [IPSS] score intermediate-1, intermediate-2, or high risk)

• Myelodysplastic syndromes (MDS) with progression to AML

• Treatment-related AML

• Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:

• In second or greater remission

• In first remission with high-risk cytogenetics [Philadelphia chromosome; t(4,11); and -7]

• Primary refractory ALL with < 10% blasts in the bone marrow

• Severe aplastic anemia that has failed immunosuppressive therapy

• Non-Hodgkin's lymphoma, meeting 1 of the following criteria:

• In second or greater remission

• Relapsed disease in a patient not eligible for autologous stem cell transplantation

• Lymphoproliferative disease (e.g., chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia), meeting 1 of the following criteria:

• In second or greater remission

• Relapsed disease in a patient not eligible for autologous stem cell transplantation

• Multiple myeloma, meeting 1 of the following criteria:

• Stage II or III disease in first or greater relapse

• Refractory disease

• Newly diagnosed disease with chromosome 13 abnormalities

• Advanced myeloproliferative disease, meeting 1 of the following criteria:

• Myelofibrosis requiring > 2 units of packed red blood cells each month

• Essential thrombocythemia or polycythemia rubra vera that has progressed to AML

• Failed prior AML therapy

• No active, uncontrolled CNS leukemia

• Not eligible for autologous or mini-allogeneic transplantation

• No fully matched or single-antigen mismatched sibling donor available

• HLA-matched unrelated donor available

• HLA typed at HLA-A, -B, -C, -DRB1 and/or -DQB1 by high-resolution techniques

• For patients without HLA identical donors, mismatches at DQ (i.e., 8/8 match) and 1 additional mismatch at the allele level at HLA-A, -B, -C, or -DRB1 (i.e., 7/8 molecular match) allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Creatinine < 2.0 mg/dL

• Pulmonary diffusing capacity > 40% of predicted

• Cardiac ejection fraction > 40% by MUGA or echocardiography

• No active liver disease

• Bilirubin = 2.0 mg/dL

• Alkaline phosphatase < 3 times upper limit of normal (ULN)

• AST < 3 times ULN

• Hepatitis C or active hepatitis B (HBV) allowed provided a liver biopsy is performed and = grade 2 inflammation is present

• Patients with active HBV viral replication must receive antiviral therapy

• HIV negative

• No ongoing active infection

• Not pregnant or nursing

• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 3 weeks since prior chemotherapy except for hydroxyurea or imatinib mesylate

• More than 3 months since prior interferon

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Biological:
• filgrastim

Drug:
• busulfan

• fludarabine phosphate

• methotrexate

• tacrolimus

Procedure:
• allogeneic bone marrow transplantation

• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality in the first 100 days post-transplant			No
Primary	Overall survival at 1 year post-transplant			No
Secondary	Incidence and severity of organ-specific toxicity			Yes
Secondary	Engraftment including neutrophil and platelet recovery and donor chimerism at 3 and 12 months post-transplant			No
Secondary	Rate of acute graft-vs-host disease (GVHD)			No
Secondary	Rate of chronic GVHD			No