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

NCT00416884 | Terminated Phase 2 Results DMC

• 3 other identifiers: CDR0000449649OHSU-TPI-02032-LOHSU-414
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia

Keywords

chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Mortality

  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.

Study Arms (1)

TBI, Campath, Fludarabine T-cell Deplete

EXPERIMENTAL

(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; Drug: Fludarabine; Radiation: Total Body Irradiation (TBI); Other: T-Cell Deplete

Interventions

Campath DRUG

30 mg on day -8 over 5-6 hours

Also known as: Nonmeylablative Stem Cell Transplant, Mini Transplant

TBI, Campath, Fludarabine T-cell Deplete

Fludarabine DRUG

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

Also known as: Nonmeylablative Stem Cell Transplant, Mini Transplant

TBI, Campath, Fludarabine T-cell Deplete

Total Body Irradiation (TBI) RADIATION

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

Also known as: Nonmeylablative Stem Cell Transplant, Mini Transplant

TBI, Campath, Fludarabine T-cell Deplete

T-Cell Deplete OTHER

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

Also known as: Nonmeylablative Stem Cell Transplant, Mini Transplant

TBI, Campath, Fludarabine T-cell Deplete

Eligibility Criteria

• Age: 4 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239-3098, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Chronic-Phase

Interventions

Alemtuzumab; fludarabine; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques

Limitations and Caveats

Study was terminated early due to low enrollment, hence the study did not have any treatment-related mortalities to report.

Results Point of Contact

• Title: Center for Hematologic Malignancies
• Organization: Center for Hematologic Malignancies

503-494-1551

Study Officials

• Richard Maziarz, MD

  OHSU Knight Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 27, 2006
• First Posted: December 28, 2006
• Study Start: May 1, 2003
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: September 27, 2017
• Results First Posted: August 2, 2011

Record last verified: 2011-07

Locations

US (1)