Flu,Alemtuzumab,and TBI Followed By Donor Stem Cell Chronic Phase CML

September 25, 2017 updated by: Richard Maziarz, OHSU Knight Cancer Institute

Fludarabine, Campath, TBI T-Cell Deplete NMSCT With Post-Transplant T-Cell Infusions for CML Failing Imatinib Therapy With Imatinib (STI571)

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation (TBI) before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and alemtuzumab, and removing the T lymphocyte cells(T cells) from the donor cells before transplant, may stop this from happening.

PURPOSE: This clinical trial is studying how well giving fludarabine, alemtuzumab, and total-body irradiation together with donor stem cell transplant and donor white blood cell (WBC) infusion works in treating patients with chronic phase chronic myelogenous leukemia (CML) that did not respond to previous imatinib mesylate.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the treatment-related mortality in patients with imatinib mesylate-resistant chronic phase chronic myelogenous leukemia treated with nonmyeloablative conditioning comprising fludarabine, alemtuzumab, and total-body irradiation followed by T-cell-depleted allogeneic stem cell transplantation and post-transplantation allogeneic T-cell infusion.
  • Determine if donor engraftment can be safely established using partial T-cell depletion with additional T-cell infusions in these patients.

OUTLINE: Patients receive alemtuzumab IV over 5-6 hours on day -8 and fludarabine IV on days -4 to -2. Patients undergo total-body irradiation followed by T-cell-depleted (CD34+ selected) allogeneic stem cell transplantation on day 0. Patients receive allogeneic T-cell infusion on days 30 and 60. Patients also receive cyclosporine twice daily beginning on day -3 and continuing until day 100 followed by a taper until day 177.

PROJECTED ACCRUAL: Not specified.

Study Type

Interventional

Enrollment (Actual)

1

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
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • OHSU Knight Cancer Institute

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

4 years to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Patients aged 4-75 with chronic myelogenous leukemia (CML) treatable by allogeneic hematopoietic stem cell transplant.

  • Patients with cytogenetically confirmed chronic phase CML.

    o Hematologic parameters for chronic phase are: i) Percentage of blasts in peripheral blood or marrow < 15% ii) Percentage of blasts + promyelocytes in the peripheral blood or bone marrow < 30% iii) Percentage of basophils in blood or marrow <20% iv) Platelet count > 100 x 109/l

  • Patients must have demonstrated refractoriness/resistance to STI571 defined as follows:

    i) Hematologically resistant- failure to achieve a complete hematologic remission (CHR) despite 3 months of STI571 therapy.

ii) Hematologically refractory - a rising WBC count > 20 x 109/l confirmed by two samples taken two weeks apart in a patient with a previous CHR despite concurrent treatment with STI571 iii) Cytogenetically resistant - bone marrow cytogenetics showing > 65% Philadelphia chromosome positivity (Ph+) after 6 months of STI571 based therapy.

iv) Cytogenetically refractory - An increase in the number of Philadelphia chromosome positive (Ph+) bone marrow cells by at least 30%, or an increase to > 65%, confirmed by samples at least 1 month apart following a previous STI571 induced cytogenetic response, while continuing STI571 therapy.

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Patients with a human leukocyte antigen (HLA) matched sibling donor at the HLA-A, B, and DR loci.
  • Patients with an unrelated hematopoietic stem cell donor must be matched using high resolution typing for class II human leukocyte antigen (HLA-DR beta-1, 3, 4, 5 and DQ beta-1) and matched with intermediate to high resolution molecular typing at class I human leukocyte antigen (HLA-A, B, and C) loci.
  • Patients with accelerated or blast crisis of CML who have returned to chronic phase as described above are eligible.
  • Written informed, voluntary consent.

Exclusion criteria:

  • Patients who have received another investigational drug within 30 days.
  • Fertile men unwilling to use contraceptive techniques during and for 24 months following treatment.
  • Females who are pregnant or fertile women unwilling to use contraceptive techniques for two months prior to entering the study and for 24 months following treatment.
  • Patients with active bacterial or fungal infections unresponsive to medical therapy.
  • Patients with organ dysfunction including cardiac ejection fraction of less than 35% or pulmonary status with a diffusing capacity of the lung for carbon monoxide(DLCO) of less than 40% and/or receiving supplemental oxygen.
  • Liver Function Abnormalities: patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, varices, history of bleeding varices, hepatic encephalopathy or chronic viral hepatitis where the total serum bilirubin is greater than 3 mg per deciliter with symptomatic biliary disease.
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.
  • Patients with a history of any prior bone marrow or peripheral blood stem cell transplantation.
  • Patients with any other serious, uncontrolled, concomitant medical condition
  • HIV positive patients

Eligibility criteria for donors:

Inclusion Criteria for Donors:

  • Sibling donors are permitted if matched at class I human leukocyte antigen (HLA-A, B), and class II human leukocyte antigen (DR) loci.
  • Unrelated donors must be matched for class II human leukocyte antigen(HLA-DR beta-1,2,3,4,5) and class II human leukocyte antigen (DQ beta-1) with high resolution typing and with intermediate resolution molecular typing at class I human leukocyte antigen(HLA-A, B, and C) loci.
  • Donors must be eligible to serve as a peripheral stem cell allograft donor. Bone marrow donors will not be permitted on this protocol.
  • Donors must be >18 and < 75 years of age.

Exclusions Criteria for Donors:

  • Volunteer donors who wish to serve as bone marrow donors only and refuse exogenous cytokines.
  • Donors who are Human immunodeficiency virus (HIV+), Human T-lymphotropic virus (HTLV-1+), or hepatitis Bs Ag+..
  • Donors with medical conditions that would result in increased risk for Granulocyte colony-stimulating factor (G-CSF) mobilization and harvest of peripheral blood stem cells (PBSC) including renal insufficiency with Cr > 2.0, idiopathic splenomegaly, underlying coagulopathy, uncontrolled coronary artery disease, and major surgery within 28 days.

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TBI, Campath, Fludarabine T-cell Deplete
(Campath) 30 mg on day -8 over 5-6 hours, Fludarabine 30 mg/m^2 on day -4 through day -2, Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0., Stem cells will be T cell depleted and given on day 0
Drug: Campath
30 mg on day -8 over 5-6 hours
Other Names:
  • Nonmeylablative Stem Cell Transplant
  • Mini Transplant
Drug: Fludarabine
Fludarabine 30 mg/m^2 on day -4 through day -2
Other Names:
  • Nonmeylablative Stem Cell Transplant
  • Mini Transplant
Radiation: Total Body Irradiation (TBI)
Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0
Other Names:
  • Nonmeylablative Stem Cell Transplant
  • Mini Transplant
Other: T-Cell Deplete
Stem cells will be T cell depleted and given on day 0
Other Names:
  • Nonmeylablative Stem Cell Transplant
  • Mini Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-related Mortality
Time Frame: lifetime followup, up to 100 years.
Treatment related mortality is a consequence of both complications of the preparative regimen and systemic immunological rejection which is manifested as graft versus host disease(GVHD). The preparative regimens which include whole body radiation and/or high dose chemotherapy are complicated by single or multi-organ failure and by prolonged myelosuppression that can lead to infections and bleeding
lifetime followup, up to 100 years.

Collaborators and Investigators

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

Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Richard Maziarz, MD, OHSU Knight Cancer Institute

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

May 1, 2003

Primary Completion (Actual)

March 1, 2008

Study Completion (Actual)

March 1, 2008

Study Registration Dates

First Submitted

December 27, 2006

First Submitted That Met QC Criteria

December 27, 2006

First Posted (Estimate)

December 28, 2006

Study Record Updates

Last Update Posted (Actual)

September 27, 2017

Last Update Submitted That Met QC Criteria

September 25, 2017

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000449649
  • OHSU-TPI-02032-L (Other Identifier: OHSU Knight Cancer Institute)
  • OHSU-414 (Other Identifier: OHSU IRB)

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.

Clinical Trials on Leukemia

Clinical Trials on Campath

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Argentina

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe