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

NCT ID: NCT00416884

Last Updated: 2017-09-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-05-31
• Study Completion Date: 2008-03-31

Brief Summary

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.

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.

Conditions

Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Campath

Intervention Type: DRUG

30 mg on day -8 over 5-6 hours

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m\^2 on day -4 through day -2

Total Body Irradiation (TBI)

Intervention Type: RADIATION

Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0

T-Cell Deplete

Intervention Type: OTHER

Stem cells will be T cell depleted and given on day 0

Interventions

Campath

30 mg on day -8 over 5-6 hours

Intervention Type: DRUG

Fludarabine

Fludarabine 30 mg/m\^2 on day -4 through day -2

Intervention Type: DRUG

Total Body Irradiation (TBI)

Total body irradiation single fraction 200 cGy at 7 cGy per minute on day 0

Intervention Type: RADIATION

T-Cell Deplete

Stem cells will be T cell depleted and given on day 0

Intervention Type: OTHER

Other Intervention Names

Nonmeylablative Stem Cell Transplant; Mini Transplant; Nonmeylablative Stem Cell Transplant; Mini Transplant; Nonmeylablative Stem Cell Transplant; Mini Transplant; Nonmeylablative Stem Cell Transplant; Mini Transplant

Eligibility Criteria

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.

• 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.

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:

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Richard Maziarz

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Maziarz, MD

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

Locations

OHSU Knight Cancer Institute

Portland, Oregon, United States

Countries

United States

Other Identifiers

OHSU-TPI-02032-L

Identifier Type: OTHER

Identifier Source: secondary_id

OHSU-414

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000449649

Identifier Type: -

Identifier Source: org_study_id