Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00296023
First received: February 23, 2006
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood 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) 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 antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.


Condition Intervention
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Biological: anti-thymocyte globulin
Biological: filgrastim
Biological: therapeutic allogeneic lymphocytes
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Low-Dose Allogeneic Peripheral Blood Stem Cell Transplantation for High-Risk Low Grade Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Toxicity and survival [ Time Frame: up to 36 months post transplant ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: January 1999
Study Completion Date: June 2008
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: stem cell transplant Biological: anti-thymocyte globulin Biological: filgrastim Biological: therapeutic allogeneic lymphocytes Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation

Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.
  • Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.

Secondary

  • Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.
  • Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.
  • Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age > 60 years).
  • Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.

OUTLINE:

  • Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.
  • Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.
  • Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.
  • Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria:

    • Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria:

      • In second or subsequent remission
      • Failed to achieve a complete remission (CR) after chemotherapy
    • Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria:

      • Low-grade NHL meeting 1 of the following criteria:

        • Standard-risk disease in second or subsequent remission
        • Standard-risk disease and failed to achieve a CR after chemotherapy
        • In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following:

          • Age > 60 years
          • Tumor stage III or IV
          • Extranodal disease at > 1 site
          • ECOG performance status ≥ 2
          • Serum lactic dehydrogenase (LDH) > upper limit of normal (ULN)
      • Intermediate- or high-grade NHL meeting 1 of the following criteria:

        • In second or subsequent remission
        • Failed to achieve a CR after initial chemotherapy
    • Waldenstrom's macroglobulinemia meeting 1 of the following criteria:

      • In second or subsequent remission
      • Failed to achieve a CR after initial chemotherapy
    • Multiple myeloma meeting 1 of the following criteria:

      • In first or subsequent remission
      • Failed to achieve a CR after initial chemotherapy
    • Myeloproliferative disorders, including any of the following:

      • Chronic myelogenous leukemia in first or subsequent chronic phase
      • Myelofibrosis
      • Essential thrombocytopenia that is poorly responsive to standard therapy
      • Polycythemia vera that is poorly responsive to standard therapy or is in spent phase
    • Prolymphocytic leukemia meeting 1 of the following criteria:

      • In first or subsequent remission
      • Failed to achieve a CR after initial chemotherapy
    • Mantle cell lymphoma meeting 1 of the following criteria:

      • In first or subsequent remission
      • Failed to achieve a CR after initial chemotherapy
    • Hodgkin's lymphoma meeting the following criteria:

      • In second or subsequent remission

        • Prior remission duration > 6 months
      • No radiation therapy as the only prior primary therapy
    • Myelodysplastic syndromes (MDS) meeting 1 of the following criteria:

      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation
      • Chronic myelomonocytic leukemia
      • Any MDS with transfusion dependence
      • Any MDS with ≥ 2 significant infections
    • Acute myeloid leukemia in morphologic remission
  • In CR or partial remission or stabilization of disease after standard chemotherapy

    • No progressive or refractory disease
  • Not eligible for standard allogeneic bone marrow transplantation
  • Meets 1 of the following criteria:

    • Age 60 to 75 years old AND no co-morbid illness
    • Younger patients with any of the following comorbidities:

      • Decreased cardiac ejection fraction
      • Pulmonary dysfunction
      • Elevated liver function tests
      • Hepatitis C infection
      • Poor performance status
  • Sibling or related donor available

    • Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • ECOG performance status 0-2
  • Creatinine < 2.0 mg/dL
  • Creatinine clearance > 40 mL/min
  • Ejection fraction > 30% by echocardiogram or MUGA
  • Bilirubin < 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal)
  • Alkaline phosphatase < 4 times ULN
  • AST < 4 times ULN
  • HIV negative
  • Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation
  • No active infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  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: NCT00296023

Locations
United States, California
Alta Bates Comprehensive Cancer Center
Berkeley, California, United States, 94704
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0324
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Thomas G. Martin, MD University of California, San Francisco
Principal Investigator: Willis Navarro, MD University of California, San Francisco
Principal Investigator: Charles A. Linker, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00296023     History of Changes
Other Study ID Numbers: CDR0000463724, UCSF-98251, UCSF-9805, UCSF-H9996-15837-06
Study First Received: February 23, 2006
Last Updated: October 2, 2012
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
noncontiguous stage II marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases
Antilymphocyte Serum
Fludarabine
Fludarabine phosphate
Methotrexate

ClinicalTrials.gov processed this record on October 21, 2014