Reduced Intensity AlloSCT in(CML) With Persistent Disease (CML)

April 12, 2011 updated by: Columbia University

A Pilot Study of Reduced Intensity Allogeneic Stem Cell Transplantation in Patients With Chronic Myeloid Leukemia (CML) and Adoptive Cellular Immunotherapy Only in Patients With Persistent Disease and Matched Family Donors

CML, a malignant disorder of stem cells, is characterized by increases in both immature and mature myeloid, erythroid, and lymphoid cells, as well as platelets in the peripheral blood. The cytogenetic hallmark of CML is the Philadelphia(Ph)chromosome found in the malignant cells of 95% of patients. CML comprises 7-20% of all leukemias with an overall incidence in the general population estimated at 1 to 2 per 100,000. The peak incidence occurs in the fifth decade, however, all age groups, including children, are affected. The only reported environmental risk factor is exposure to excessive ionizing radiation that is documented in only a very small percentage of patients. Clinically, CML is characterized by an initial chronic phase in which patients may report mild constitutional symptoms; however, 40-50% are asymptomatic and are diagnosed based upon abnormal blood counts discovered during a routine examination. The chronic phase typically lasts three to five years, and is followed by an accelerated phase distinguished by progressive systemic symptoms, an increasing resistance to conventional chemotherapy, and a rise in the peripheral blood and bone marrow blast count. This evolves rapidly into a blastic crisis characterized by immature cells resembling the blasts characteristic of acute leukemia. The presence of 30% or more blastic cells in the blood or marrow is diagnostic of this final blastic phase which is typically fatal within 3 to 6 months.

The primary treatment options for CML have traditionally been monotherapy with either busulfan or hydroxyurea. Both agents are able to control the clinical symptoms associated with CML, as well as induce hematological remissions in 80% of chronic phase patients. However, complete cytogenetic remissions with either agent are rare, and neither is able to prevent eventual progression to the terminal blastic phase; therefore, these therapies can only be considered palliative.

The primary purpose of this clinical research trial is to study the feasibility of a reduced intensity allogenic transplant for CML. This study will also determine the side effects as well as the response rate.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Further study details will be provided by Columbia University, Division of Pediatric Blood and Marrow Transplantation.

STUDY DESIGN:

Patients less than 30 years of age with CML in 1st or 2nd chronic phase or 1st accelerated phase and a matched related donor, an unrelated cord blood donor, or an unrelated adult donor, will receive 6 days of IV Fludarabine, 4 doses of IV Busulfex, and 5 doses of Alemtuzumab. Patients with persistant RT-PCR positive BCR-Abl and/or Philadelphia chromosome positivity by cytogentics after Day + 100 and a matched related donor would receive DLIx1. If still BCR-Abl or Philadelphia chromosome positive at Day +180 and a matched related donor, patients would receive a second dose of DLI. All patients will receive STI-571 (Gleevec) after hematological reconstitution. Studies for immune reconstitution, chimersim, and MRD will be performed postt AlloSCT.

Study Type

Interventional

Enrollment (Actual)

5

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
    • New York
      • New York, New York, United States, 10032
        • Morgan Stanley Children's Hospital of NYP

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

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age: Patient must be less than 30 years of age.
  • Consent: Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services.
  • Organ Function: Patient must have adequate organ function as below Adequate renal function defined as:Serum creatinine 1.5 x normal, or Creatinine clearance or radioisotope GFR > 40 ml/min/m2 or >60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
  • Adequate liver function defined as:Total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal

  • Adequate cardiac function defined as:

    • Shortening fraction of >25% by echocardiogram, or
    • Ejection fraction of >40% by radionuclide angiogram or echocardiogram

  • Adequate pulmonary function defined as:

    -DLCO >40% by pulmonary function test For children who are uncooperative, no evidence of dyspnea at rest,no exercise intolerance, and a pulse oximetry >94% in room air.

  • Disease Status

    • Patients with CML with either of the following:
    • Patients in 1st or 2nd chronic phase
    • Patients in 1st or 2nd accelerated phase

Exclusion Criteria:

  • Patient in blast crisis
  • Patient in 3rd or greater chronic phase

  • Patient in 3rd or greater accelerated phase

    • women that are pregnant are ineligible

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Matched Family Donor
Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine
Busulfan and Fludarabine
Other Names:
  • RIC
Experimental: Unrelated Donor
Unrelated Donor Transplant/ Cord Blood Transplant
Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine
Busulfan and Fludarabine
Other Names:
  • RIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML.
Time Frame: Until Study End
Until Study End

Collaborators and Investigators

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

Sponsor

Columbia University

Investigators

  • Principal Investigator: Mtchell S Cairo, MD, Columbia University

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

January 1, 2003

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

September 15, 2007

First Submitted That Met QC Criteria

September 17, 2007

First Posted (Estimate)

September 18, 2007

Study Record Updates

Last Update Posted (Estimate)

April 14, 2011

Last Update Submitted That Met QC Criteria

April 12, 2011

Last Verified

April 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAA8191
  • CHNY-01-505 (Other Identifier: CU)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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