Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Levine, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00143845
First received: August 31, 2005
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to determine whether a reduced intensity conditioning regimen for stem cell transplant with donor cells will allow the donor cells to be effective without causing health problems.


Condition Intervention Phase
Multiple Myeloma
Lymphocytic Leukemia, Chronic
Lymphoma, Low-Grade
Procedure: Reduced intensity conditioning
Procedure: Rapid immunosuppressive taper
Procedure: Prophylactic donor leukocyte infusions
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Adjuvant Cellular Immunotherapy for High-Risk Hematologic Malignancy After Reduced Intensity Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4 [ Time Frame: 100 days ] [ Designated as safety issue: No ]

    The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows:

    Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement


  • Percentage of Participants With Progression Free Survival [ Time Frame: two years ] [ Designated as safety issue: No ]

    The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies.

    We define disease progression as disease recurrence within 180 days of transplant.



Secondary Outcome Measures:
  • To Evaluate Surrogate Markers of GVHD and Correlate These With Clinical Outcomes During the Above Trial [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Enrollment: 54
Study Start Date: April 2003
Study Completion Date: February 2013
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immunosuppression Taper
Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).
Procedure: Reduced intensity conditioning
Busulfan and Fludarabine regimen
Procedure: Rapid immunosuppressive taper
Taper of Tacrolimus, Methotrexate and Mycophenolate Mofetil
Procedure: Prophylactic donor leukocyte infusions
If the patient has GVHD overall grade 0-1 or skin grade 1 on day +100, then 5 x 107 CD3+ cells/kg recipient weight are given.

Detailed Description:

In this research study patients will receive dosages of chemotherapy that are lower than the usual dosages. The study will determine whether a shorter duration of immunosuppression will permit the donor cells to be effective against the cancer without causing more severe GVHD (Graft Versus Host Disease). Also to be determined is whether the patient's cancer can be prevented from relapsing after blood stem cell transplant by using prophylactic treatment, giving a donor leukocyte infusion BEFORE a relapse happens.

In this research study samples of blood and bone marrow will be analyzed. These samples will be examined to study the cellular production of inflammatory cytokine levels in attempt to be able to predict which patients will have complications like GVHD or relapse.

  Eligibility

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

Patient Inclusion Criteria:

To be eligible a patient MUST meet at least one of the next 4 criteria

  • Any patient aged 55 years or older with a hematological malignancy for which allogeneic transplant is considered an appropriate treatment, AND/OR
  • Any patient, regardless of age, with a hematologic malignancy for which allogeneic transplant is considered an appropriate treatment and the patient is not eligible for a conventional myeloablative transplant because of organ dysfunction AND/OR
  • Any patient, regardless of age, who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy AND/OR
  • Any patient, regardless of age, with one of the following hematological malignancies:

    1. Multiple myeloma

      1. refractory to or failure following conventional chemotherapy such as VAD (Vincristine, Adriamycin and Dexamethasone), pulse decadron, or alkylating agents, or
      2. chromosomal abnormality associated with poor prognosis by cytogenetics or FISH probe.
    2. Chronic lymphocytic leukemia patients, Rai stage 3 or 4 and relapsed following/refractory to alkylating agents or nucleoside analog therapy
    3. Low grade lymphoma (small lymphocytic, follicular small cleaved cell, or follicular mixed small cleaved and large cell) that is either relapsed or refractory provided the disease is NOT rapidly progressive, NOT bulky, and no mass exceeds 5 cm in greatest dimension.

To be eligible a patient MUST meet all of the following criteria

  • In addition to the above criteria ALL patients must meet the following minimum organ function:

    1. Cardiac: Ejection fraction at least 30%.
    2. Renal: Adequate renal function as defined by creatinine < 2.0mg OR creatinine clearance >40 mg/min by 24-hour urine collection or GFR (Glomerular Filtration Rate. (Gender and age-adjusted creatinine clearance >40ml/min by Gault-Cockroft 55 is acceptable for adults: (140 - age) x weight/72 x Scr [x 0.85 if female]).
    3. Pulmonary: FEV1 and FVC >60%.
    4. Hepatic: Total bilirubin <2.0 and AST (Aspartate Aminotransferase)/ALT (Alanine Transaminase) < 3X institutional normal for age.
    5. Performance (adults): Karnofsky score must be at least 60; for pts. under 16, Lansky score must be at least 60.
  • Availability of a 5/6 or 6/6 HLA A, B, and DR identical relative who is willing and able to donate allogeneic stem cells. Serological, low resolution or mid resolution molecular typing will determine the degree of match for HLA (Human Leukocyte Antigen) class I regardless of high resolution DNA typing results. High resolution typing will be used to determine the degree of match for HLA-DR.
  • No untreated or uncontrolled invasive infections. Patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic and/or culture) that the infection is well controlled. Patients under treatment for infection will be enrolled only after clearance from the Principal Investigator.
  • Not pregnant

Patient Exclusion Criteria:

  • acute leukemia
  • HIV positive patients not eligible
  • Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient
  • Pregnant

Donor Inclusion Criteria:

  • 5/6 or 6/6 HLA match for HLA-A, B, and DR
  • Age 3-70 years, good general health
  • No contraindication to G-CSF (Granulocyte Colony-Stimulating Factor)stimulation
  • No contraindication to leukapheresis of peripheral blood stem cells
  • Good general health

Donor Exclusion Criteria:

  • HIV positive or history of HIV risk factors
  • Presence of other diseases transmissible by blood that pose unacceptable risk to the study subject.
  • Pregnant
  • Medical or psychological conditions that would make the donor unlikely to tolerate G-CSF - injections or leukapheresis
  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: NCT00143845

Locations
United States, Michigan
The University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: John E. Levine, MD, MS The Univeristy of Michigan
  More Information

No publications provided

Responsible Party: John Levine, MD, Professor of Pediatrics and Communicable Diseases and Professor of Internal Medicine, Medical School, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00143845     History of Changes
Other Study ID Numbers: UMCC 2-61
Study First Received: August 31, 2005
Results First Received: May 19, 2014
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Disease Attributes
Pathologic Processes
Immunosuppressive Agents
Mycophenolate mofetil
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014