Reduced Intensity AlloSCT in(CML) With Persistent Disease

NCT00531310 | Terminated Phase 2 DMC

• 2 other identifiers: AAAA8191CHNY-01-505
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myeloid Leukemia

Keywords

CML; allogeneic SCT; matched family donor; unrelated donor; cord blood donor; persistent disease

Outcome Measures

Primary Outcomes (1)

• To determine the toxicity associated with reduced intensity therapy and allogeneic SCT in selected patients with CML.

  Until Study End

Study Arms (2)

Matched Family Donor

EXPERIMENTAL

Matched Family Donor

Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine

Unrelated Donor

EXPERIMENTAL

Unrelated Donor Transplant/ Cord Blood Transplant

Drug: Reduced Intensity Conditioning, Busulfan and Fludarabine

Interventions

Reduced Intensity Conditioning, Busulfan and Fludarabine DRUG

Busulfan and Fludarabine

Also known as: RIC

Matched Family Donor; Unrelated Donor

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Patient in blast crisis
• Patient in 3rd or greater chronic phase
• Patient in 3rd or greater accelerated phase
• women that are pregnant are ineligible

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Morgan Stanley Children's Hospital of NYP

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Busulfan; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Mtchell S Cairo, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 15, 2007
• First Posted: September 18, 2007
• Study Start: January 1, 2003
• Primary Completion: December 1, 2007
• Study Completion: June 1, 2010
• Last Updated: April 14, 2011

Record last verified: 2011-04

Locations

US (1)