Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Malignancies or Secondary Myelodysplasia Previously Treated With High-Dose Chemotherapy and Autologous Stem Cell Transplant

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01118013
First received: May 5, 2010
Last updated: July 9, 2015
Last verified: July 2015
  Purpose

RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .


Condition Intervention Phase
Leukemia
Lymphoma
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: anti-thymocyte globulin
Biological: donor lymphocytes
Biological: filgrastim
Biological: therapeutic allogeneic lymphocytes
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: tacrolimus
Other: reduced-intensity transplant conditioning procedure
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Monoblastic Leukemia Acute Myeloblastic Leukemia With Maturation Acute Myeloblastic Leukemia Without Maturation Acute Myeloid Leukemia Acute Myelomonocytic Leukemia Acute Non Lymphoblastic Leukemia Acute Promyelocytic Leukemia Anaplastic Large Cell Lymphoma Anaplastic Plasmacytoma B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Cutaneous T-cell Lymphoma Di Guglielmo's Syndrome Follicular Lymphoma Hodgkin Lymphoma Hodgkin Lymphoma, Childhood Juvenile Myelomonocytic Leukemia Leukemia, B-cell, Chronic Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myeloid Leukemia Plasmablastic Lymphoma Sezary Syndrome Small Non-cleaved Cell Lymphoma Squamous Cell Carcinoma of the Head and Neck
U.S. FDA Resources

Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Event-free survival (EFS) [ Time Frame: Up to 5.5 years ] [ Designated as safety issue: No ]
  • Comparison of EFS distribution to that of CALGB-100002 [ Time Frame: Up to 5.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: Up to 5.5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5.5 years ] [ Designated as safety issue: No ]
  • Rate of opportunistic infections [ Time Frame: Up to 5.5 years ] [ Designated as safety issue: No ]
  • Graft-versus-host disease at 6 months [ Time Frame: at 6 months ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: December 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60.

Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.

Biological: anti-thymocyte globulin Biological: donor lymphocytes Biological: filgrastim Biological: therapeutic allogeneic lymphocytes Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: tacrolimus Other: reduced-intensity transplant conditioning procedure Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed hematologic malignancies:

    • Chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL)

      • Absolute lymphocytosis of > 5,000/μL
      • Lymphocytes must appear morphologically mature with < 55% prolymphocytes (CLL)

        • Patients with > 55% prolymphocytes are considered as having PLL
      • Lymphocyte phenotype with expression of CD20, CD19, and CD5 (CLL)
    • Non-Hodgkin lymphoma

      • Any WHO classification of histologic subtype
      • Core biopsies acceptable for primary diagnosis and immunophenotyping
      • Bone marrow biopsies as sole means of diagnosis not allowed for follicular lymphoma
    • Hodgkin lymphoma

      • Any WHO classification of histologic subtype
      • Core biopsies acceptable for primary diagnosis and immunophenotyping
      • Bone marrow biopsy is required
    • Multiple myeloma

      • Patients must have active disease requiring treatment (Durie-Salmon stage I-III)
    • Acute myeloid leukemia

      • Must have < 10% bone marrow blasts and no circulating blasts
    • Myelodysplastic syndrome (MDS)

      • MDS as define by WHO criteria
      • Must have < 10% marrow blasts
  • Relapsed or progressive disease or myelodysplasia ≥ 6 months after prior high-dose chemotherapy with autologous hematopoietic cell support

    • Prior syngeneic transplantation allowed
  • Healthy donor meeting one of the following criteria:

    • HLA-identical sibling (6/6)

      • Serologic typing for class I (A, B) and molecular typing for class II (DRB1) required
    • 8/8 matched-unrelated donor

      • Molecular identity at HLA A, B, C, and DRB1 by high-resolution typing required
    • No syngeneic donors

PATIENT CHARACTERISTICS:

  • Creatinine clearance ≥ 40 mL/min
  • Total bilirubin ≤ 2 mg/dL
  • AST ≤ 3 times upper limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • DLCO ≥ 40% with no symptomatic pulmonary disease
  • LVEF ≥ 30% by MUGA or ECHO
  • No uncontrolled diabetes mellitus or active serious infection
  • No known hypersensitivity to E.coli-derived products
  • No HIV infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 4 weeks should elapse between prior standard cytotoxic chemotherapy, radiation therapy, or surgery and the planned start of the preparative regimen on day -7
  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: NCT01118013

Locations
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Florida
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Principal Investigator: Asad Bashey, MD, PhD Blood and Marrow Transplant Group of Georgia
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01118013     History of Changes
Other Study ID Numbers: CALGB-100601, CALGB-100601, CDR0000667954
Study First Received: May 5, 2010
Last Updated: July 9, 2015
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
juvenile myelomonocytic leukemia
prolymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
recurrent childhood acute myeloid leukemia
refractory chronic lymphocytic leukemia
recurrent adult Hodgkin lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma

Additional relevant MeSH terms:
Lymphoproliferative Disorders
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Neoplasms by Histologic Type
Paraproteinemias
Precancerous Conditions
Vascular Diseases
Antilymphocyte Serum
Fludarabine
Fludarabine phosphate
Methotrexate
Mycophenolate mofetil
Mycophenolic Acid
Abortifacient Agents
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on September 03, 2015