DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Information source: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes

Intervention: anti-thymocyte globulin (Biological); sargramostim (Biological); therapeutic allogeneic lymphocytes (Biological); busulfan (Drug); fludarabine phosphate (Drug); methotrexate (Drug); tacrolimus (Drug); nonmyeloablative allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: UNC Lineberger Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Thomas C. Shea, MD, Principal Investigator, Affiliation: UNC Lineberger Comprehensive Cancer Center

Summary

RATIONALE: Giving low doses of chemotherapy, such as busulfan and fludarabine, before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease. PURPOSE: This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease.

Clinical Details

Official title: Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment With a More Intensive Therapeutic Regimen

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Treatment-related mortality

Secondary outcome:

Complete response at 6 and 12 months post-transplant

Complete or mixed donor chimerism at 30, 60, and 90 days post-transplant

5-year disease-free survival

Graft-vs-host disease at 6 months post-transplant

Detailed description: OBJECTIVES: Primary

- Determine the clinical efficacy and toxicity profiles of a nonmyeloablative preparative

regimen comprising busulfan and fludarabine with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation in patients with hematologic cancers or other diseases.

- Determine the feasibility of this regimen in these patients.

- Establish a treatment-related mortality during the first 6 months that is less than 20%

in patients treated with this regimen. Secondary

- Determine the response rates (disease-specific partial response and complete response)

in patients treated with this regimen.

- Determine overall and progression-free survival of patients treated with this regimen.

- Determine the percent donor chimerism and immunologic recovery, including dendritic

cell recovery, in patients treated with this regimen.

- Determine the risk of acute and chronic graft-versus-host disease and other toxicities

in patients treated with this regimen.

- Assess the overall nonhematologic grades 3 and 4 toxicity of this regimen, including

the incidence of veno-occlusive disease and pulmonary toxicity, in these patients. OUTLINE: Patients are assigned to 1 of 4 treatment groups according to disease type and donor type.

- Preparative regimen:

- Group 1 (patients with acute myeloid leukemia [AML], acute lymphoblastic leukemia

[ALL], IPSS [International Prognostic Scoring System score] high-risk myelodysplastic syndromes [HR MDS], or chronic myelogenous leukemia [CML] with an HLA-matched related donor [MRD]): Patients receive fludarabine phosphate IV over

30 minutes on days - 7 to -3 and busulfan IV continuously over 48 hours on days -6

and - 5.

- Group 2 (patients with AML, ALL, IPSS HR MDS, or CML with an HLA-matched unrelated

donor [MUD] or mismatched related donor [MMRD]): Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours

on day - 8.

- Group 3 (patients with all other diseases with a MRD): Patients receive

fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin as in group 2.

- Group 4 (patients with all other disease with a MUD or MMRD): Patients receive

fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV

over 4 hours on days - 8 and -7.

- Allogeneic stem cell transplantation: All patients undergo allogeneic peripheral blood

stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously once daily beginning on day 5 (groups 1 and 2) or day 7 (groups 3 and 4) and continuing until blood counts recover.

- Graft-vs-host disease (GVHD) prophylaxis: All patients receive oral tacrolimus twice

daily on days - 1 to 120 followed by a taper until day 180. Patients in groups 1 and 2

also receive methotrexate IV on days 1, 3, and 6.

- Donor lymphocyte infusion (DLI): After day 120, patients with progressive disease or

stable disease while off immunosuppression and with no evidence of active GVHD may receive DLI. Treatment with DLI may repeat every 8 weeks for up to 3 total infusions in the absence of disease response or GVHD. Peripheral blood and/or bone marrow samples are collected at baseline and then at 30, 60, 90, 120, and 180 days post-transplantation. Chimerism (including the following subsets: whole blood, T-cells as defined by CD3 positivity, B-cells as defined by CD19 positivity, and myeloid cells as defined by CD14 and CD15 positivity) is analyzed by polymerase chain reaction technology. After restaging between Days 90 and 100 and between Days 150 to 180, patients are followed every 6 months for 1 years and then yearly for a maximum of 5 years from study entry.

Eligibility

Minimum age: 10 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Chronic lymphocytic leukemia (CLL), meeting the following criteria:

- Absolute lymphocyte count > 5,000/mm³

- Lymphocytes must appear morphologically mature with < 55% prolymphocytes

- Lymphocyte phenotype with expression of CD19 and CD5

- Prolymphocytic leukemia (PLL), meeting the following criteria:

- Absolute lymphocyte count > 5,000/mm³

- More than 55% prolymphocytes

- Morphologically diagnosed

- Chronic myelogenous leukemia (CML), meeting the following criteria:

- Diagnosis of CML or similar myeloproliferative disorders based on t(9;22)

or related t(9;12) cytogenetic abnormalities AND characterized by elevated WBC counts in peripheral blood or bone marrow

- In first chronic phase CML and a candidate for treatment with reduced-dose

busulfan

- Patients with other cytogenetic abnormalities, such as t(9;12), that are

associated with an aggressive clinical course are eligible

- Non-Hodgkin's lymphoma (NHL), meeting the following criteria:

- Any WHO class histologic subtype allowed

- Core biopsies are acceptable provided they contain adequate tissue for

primary diagnosis and immunophenotyping

- Bone marrow biopsies as sole means of diagnosis are not allowed for

follicular lymphoma

- Hodgkin's lymphoma, meeting the following criteria:

- Any WHO class histologic subtype allowed

- Core biopsies are acceptable provided they contain adequate tissue for

primary diagnosis and immunophenotyping

- Multiple myeloma, meeting the following criteria:

- Active disease requiring treatment (Durie-Salmon stages I, II, or III)

- Acute myeloid leukemia with documented control, defined as < 10% bone marrow

blasts and no circulating blasts

- Acute lymphoblastic leukemia, meeting the following criteria:

- In early first relapse or beyond OR in first complete remission and has 1

of the following high-risk features:

- t(9;22) or t(4;11)

- WBC count > 30,000/mm³ at presentation

- Non-T-cell phenotype

- More than 30 years of age

- Agnogenic myeloid metaplasia/myelofibrosis

- Patients who are transfusion dependent or who have evolving myelodysplastic

or leukemic features or high-risk cytogenetic abnormalities are eligible

- Myelodysplastic syndromes (MDS) as defined by WHO criteria

- Meets 1 of the following criteria:

- Over 55 years of age

- Ineligible for busulfan-based therapy based on diminished organ function or poor

performance status

- Indolent and chemotherapy-responsive CLL, low-grade NHL, small lymphocytic

lymphoma, or PLL

- Patients who have undergone prior autologous stem cell transplantation are

preferentially enrolled on clinical trial CALGB-100002, if available and patient is eligible

- HLA-matched or mismatched related donor or HLA-matched unrelated donor available

- HLA-identical sibling (6/6 or 9/10) (minimal serologic typing required for class

I [A, B]; molecular typing required for class II [DRB1])

- 9/10 matched unrelated donor (MUD) (molecular analysis at HLA A, B, C, DRB1, and

DQB1 by high resolution typing required)

- 5/6 MUD (molecular analysis at HLA A, B, and DRB1 required)

- No syngeneic donors

PATIENT CHARACTERISTICS:

- Creatinine clearance ≥ 40 mL/min

- Bilirubin ≤ 3 times upper limit of normal (ULN)

- AST ≤ 3 times ULN

- DLCO > 40% with no symptomatic pulmonary disease

- LVEF ≥ 30% by MUGA

- No uncontrolled diabetes mellitus or active serious infection

- No known hypersensitivity to Escherichia coli-derived products

- No HIV infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior chemotherapy, radiotherapy (except prophylactic cranial

x-ray therapy), or surgery

Locations and Contacts

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: November 2003
Last updated: June 16, 2014

Page last updated: August 20, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017