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PR1-Specific Cytotoxic T-Lymphocyte Infusion With Recurrent Chronic Myelogenous Leukemia (CML) After Allogeneic Hematopoietic Transplantation

This study has been withdrawn prior to enrollment.
(Study failed to accrue any patients due to regulatory issues with PR1 vaccine and T cell production.)
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00866346
First received: March 18, 2009
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

Primary Objective:

To determine the maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL) as treatment for relapsed or persistent chronic myelogenous leukemia (CML) after allogeneic hematopoietic transplantation from an HLA-matched related or unrelated donor.

Secondary Objectives:

  1. To evaluate the immunological response following PR1-CTL treatment
  2. To evaluate the clinical efficacy by determining clinical, cytogenetic and molecular response rates within 6 months

Condition Intervention Phase
Chronic Myelogenous Leukemia
Biological: PR1-primed lymphocyte (PR1-CTL) Infusion
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of PR1-Specific Cytotoxic T-Lymphocyte Infusion for Patients With Recurrent CML After Allogeneic Hematopoietic Transplantation

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximally tolerated dose of donor PR1-specific cytotoxic T-lymphocytes (PR1-CTL) [ Time Frame: Continuous reassessment, infusion day 0 and second infusion day 60+/- 7 ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: March 2008
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PR1-CTL

Two infusions of PR1-specific T lymphocytes (donor immune cells) 60 days apart.

Starting infusion dose 1 x 106 nucleated cells/kg.

Biological: PR1-primed lymphocyte (PR1-CTL) Infusion

Two infusions of PR1-specific T lymphocytes (donor immune cells) 60 days apart.

Starting infusion dose 1 x 106 nucleated cells/kg.

Other Names:
  • AHT
  • Allogenic Hemotopoietic Transplantation
  • PR1-CTL

Detailed Description:

Before treatment starts, you will have a complete physical exam, including blood (about 2 tablespoons) tests. You will have a chest x-ray and bone marrow will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test.

You will be treated with donor immune cells (T lymphocytes) that will specifically target certain leukemia cells in your body. Each participant will receive two doses of donor cells, 60 days apart. The second dose will be given 60 days after the first dose, at a higher dose level, as long as no serious side effects occur after the first dose and there is still disease present. Four dose levels of PR1-specific T lymphocytes will be considered. Up to 30 patients will be treated in cohorts of 3, starting at the lowest dose level, and not skipping an untried dose level when escalating. The trial will be stopped early if the lowest dose level is found to be unacceptably toxic.

These cells will be given on an outpatient basis. After each donor cell infusions, you will be followed once a week in the outpatient clinic for at least 1 month and then every 3 months for at least one year. You will have routine blood (about 2 tablespoons) and urine tests at these visits. Participants experiencing side effects from their leukemia or leukemia treatment may need to be hospitalized earlier.

You will also receive several other medications to help decrease the risk of infections while your immune system is weak. These include preventative antibiotics, antiviral drugs, and antifungal drugs.

Bone marrow samples will be taken before the second cell infusion, and then 8 weeks, 12 weeks, 6 months and 1 year after the second cell infusion.

This is an investigational study. A total of up to 30 patients will be take part in this study. All will be enrolled at UTMDACC.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with chronic myelogenous leukemia (CML) who have previously undergone allogeneic hematopoietic transplantation and have evidence of disease, as defined by a,b or c (a) >5% Philadelphia chromosome positive cells on cytogenetic studies >/= 3 months post-transplant
  2. (b) For patients in cytogenetic remission post-transplant, molecular evidence of disease at any time, defined as recurrence of quantitative PCR positivity for bcr-abl after achieving a molecular remission confirmed by 2 assays, 3 months apart or sooner if clinically indicated; OR a >10-fold increase in the relative expression of bcr-abl/abl detected and confirmed by a minimum of 2 consecutive PCR analysis, 3 months apart or sooner
  3. (c) Molecular evidence of persistent disease on Real time PCR (bcr-abl/ abl x 100 of 0.05 and not declining) >3 months post-transplantation after treatment with imatinib mesylate.
  4. Patients must have an HLA compatible related or unrelated donor capable of donating peripheral blood stem cells using apheresis techniques. This must be the same donor used for the original allogeneic hematopoetic transplantation. Patient must be HLA-A2 positive
  5. ECOG performance status < or = 2
  6. Serum bilirubin < or = 2 mg/dl
  7. Serum transaminases < 4 x normal
  8. Serum creatinine < or = 2 mg/dl
  9. No active uncontrolled infection
  10. HIV negative
  11. No acute and/or chronic GVHD requiring systemic steroid therapy
  12. Patient is not pregnant or breast feeding.
  13. Signed informed consent
  14. Patients must be off all immunosuppressive medications for at least 2 weeks prior to study entry.

Exclusion Criteria:

None.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866346

Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Muzaffar H. Qazilbash, MD UT MD Anderson Cancer Center
Study Chair: Richard E. Champlin, MD, BS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00866346     History of Changes
Other Study ID Numbers: 2003-0564, NCI-2012-01651
Study First Received: March 18, 2009
Last Updated: March 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia
CML
Allogeneic Hematopoietic Transplantation
Bone Marrow Transplant
PR1-Specific Cytotoxic T-Lymphocyte Infusion

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 24, 2014