Reduced Intensity AlloSCT in(CML) With Persistent Disease

This study has been terminated.
(Poor accrual)
Sponsor:
Information provided by:
Columbia University
ClinicalTrials.gov Identifier:
NCT00531310
First received: September 15, 2007
Last updated: April 12, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Chronic Myeloid Leukemia
Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML. [ Time Frame: Until Study End ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: January 2003
Study Completion Date: June 2010
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Matched Family Donor
Matched Family Donor
Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine
Busulfan and Fludarabine
Other Name: RIC
Experimental: Unrelated Donor
Unrelated Donor Transplant/ Cord Blood Transplant
Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine
Busulfan and Fludarabine
Other Name: RIC

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00531310

Locations
United States, New York
Morgan Stanley Children's Hospital of NYP
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Mtchell S Cairo, MD Columbia University
  More Information

No publications provided

Responsible Party: Mitchell Cairo, MD, Columbia University
ClinicalTrials.gov Identifier: NCT00531310     History of Changes
Other Study ID Numbers: AAAA8191, CHNY-01-505
Study First Received: September 15, 2007
Last Updated: April 12, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
CML
allogeneic SCT
matched family donor
unrelated donor
cord blood donor
persistent disease

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Busulfan
Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on April 22, 2014