Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan

June 26, 2017 updated by: University of California, Davis

This is a Phase II trial designed to evaluate the efficacy and toxicity of RIST, conditioned with fludarabine and busulfan, using G-CSF mobilized PBSC from an HLA-matched sibling or an unrelated volunteer donor. The primary endpoint of this study is day 100 TRM (Treatment Related Mortality). Secondary endpoints include response, engraftment times, acute and chronic GVHD, chimerism, toxicities, progression-free survival and overall survival.

Objectives

To assess the efficacy and toxicity of Reduced Intensity Transplant (RIST) for patients with hematological malignancies, conditioned with fludarabine (Fludara®) and busulfan intravenous (Busulfex™).
To evaluate progression-free survival and overall survival.
To determine donor chimerism.
To assess the risk of acute and chronic graft versus host disease (GVHD).

Study Overview

Status

Completed

Conditions

Hematologic Malignancies

Intervention / Treatment

Procedure: Reduced Intensity Stem Cell Transplantation

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- California
  - Sacramento, California, United States, 95817
    - University of CA, Davis Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

• Diagnosed with (any of the following)

Disease Subtype Disease Status Leukemia Acute myelogenous leukemia (AML) Recurrent disease in remission* OR CR1 with poor-risk cytogenetics, antecedent hematological disease (i.e. myelodysplasia) or treatment-related leukemia Acute lymphoblastic leukemia (ALL) Recurrent disease in remission* OR CR1 with Philadelphia chromosome or poor risk cytogenetics Chronic myelogenous leukemia (CML) First or second chronic phase. There must be documented disease progression after imatinib mesylate (Gleevec) therapy OR documented lack of cytogenetic response 6 months post-imatinib initiation OR imatinib intolerance.

Patient - Inclusion criteria (Continued) Chronic lymphocytic leukemia (CLL) Recurrent disease after fludarabine-based therapy. Patients must have chemosensitive** disease at the time of relapse.

Lymphoma Recurrent Hodgkin's Lymphoma

Recurrent Non-Hodgkin's lymphoma (NHL) (Low, intermediate or high grade)

Transformed NHL Patients must have had prior autologous transplantation and received cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop

Patient with relapsed disease and required >2 salvage regimens to achieve CR or CRu.

Multiple Myeloma Recurrent Myeloma Patients must have had prior autologous transplantation and demonstrate chemosensitivity** at the time of relapse Myelodysplastic Syndrome # RA/RARS RCMD/RCMD-RS RAEB-1 Patients must be transfusion-dependent and have International prostate symptom score (IPSS) of 1.5 or higher Advanced myeloproliferative disease Myelofibrosis with myeloid metaplasia; primary or evolved from other MPD Patient must be transfusion dependent or have evidence of progressive organomegaly or evidence of myelodysplasia

remission is defined as morphological remission with bone marrow aspirate/biopsy showing <= 5% blasts within 4 weeks before the start of therapy. (Cytogenetic or molecular remission is not required)
- In CLL, chemosensitivity is defined as greater than 50% reduction of wbc and lymphadenopathy. In MM, it is defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration.
  - based on WHO classification system. Patients with RAEB-2 or del(5q) are excluded
    - 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor
    - Age > 50 OR age 18-50, but have preexisting medical conditions, or have received prior therapy (i.e. prior) autologous transplantation) and are considered to be a too high a risk for conventional myeloablative transplantation

Exclusion Criteria:

• Karnofsky performance status of less than 50%
- Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
- Corrected pulmonary-diffusing capacity of less than 35%
- A cardiac ejection fraction of less than 30%
- A serologic evidence of infection with the human immunodeficiency virus
- Inability to give informed consent
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
- Decompensated liver disease with serum bilirubin > 2.0 mg/dl
- Serum creatinine > 2.0 mg/dl
- Uncontrolled active infection
- Uncontrolled CNS metastasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the efficacy and toxicity of Reduced Intensity Transplant (RIST) for patients with hematological malignancies, conditioned with fludarabine (Fludara®) and busulfan intravenous (Busulfex™) Time Frame: 3 years	3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2007

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

February 12, 2009

First Submitted That Met QC Criteria