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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 terminated.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01118013
First received: May 5, 2010
Last updated: February 6, 2017
Last verified: February 2017
May 5, 2010
February 6, 2017
December 2010
March 2012   (Final data collection date for primary outcome measure)
  • Event-free Survival (EFS) [ Time Frame: Duration of study (up to 5.5 years) ]
    EFS was defined as the date of transplant to date of progression or develop myelodysplasia after autologous transplant. EFS was estimated using the Kaplan Meier method.
  • Comparison of EFS Distribution to That of CALGB-100002 [ Time Frame: 2 years ]
    EFS distributions between CALGB-100002 and this study will be compared using the two-sample log-rank test.
  • Event-free Survival (EFS)
  • Comparison of EFS Distribution to That of CALGB-100002
Complete list of historical versions of study NCT01118013 on ClinicalTrials.gov Archive Site
  • Complete Response Rate [ Time Frame: Up to 5.5 years ]
    Complete response (CR) rate is reported as the percentage of participants who achieved a CR.
  • Overall Survival [ Time Frame: Up to 5.5 years ]
    Overall survival (OS) was defined as the transplant from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% confidence interval (CI) was estimated using the Kaplan Meier method.
  • Rate of Opportunistic Infections [ Time Frame: 1 year post transplant ]
    Percent of participants who have an opportunistic (viral, bacterial and fungal) infection in the first year following transplant.
  • Complete Response Rate
  • Complete (> 90%) or mixed donor chimerism
  • Overall Survival
  • Rate of Opportunistic Infections
  • Graft-versus-host disease at 6 months
Not Provided
Not Provided
 
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
Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation

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 .

OBJECTIVES:

Primary

  • To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic hematopoietic cell transplantation in patients with relapsed hematologic malignancies or secondary myelodysplasia after completion of prior high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
  • To compare the strategy of this regimen with the strategy used in CALGB-100002.

Secondary

  • To describe the response rate at 6 and 12 months in patients treated with this regimen.
  • To describe the time-to-progression in patients treated with this regimen.
  • To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within 20% of target AUC in > 80% of patients.
  • To determine percent of donor chimerism in T-cell, myeloid and B-cell populations achieved with this regimen compared with CALGB-100002.
  • To determine the risk of acute and chronic graft-versus-host disease and other toxicities of this regimen in these patients.
  • To describe the overall survival and disease-free survival of patients treated on this regimen.
  • To determine the rate of viral, bacterial, and fungal opportunistic infections occurring in the first year after transplantation compared with CALGB-100002.

OUTLINE: This is a multicenter study.

  • Preparative Regimen:

    • Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days -14 and -9.
    • Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
  • Graft-vs-Host Disease (GVHD) Prophylaxis:

    • HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper* as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.

NOTE: * Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is < 50% at day 60 or patient has progressive disease.

  • 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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
  • 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
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.

Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
August 2013
March 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 69 Years   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01118013
CALGB-100601
CALGB-100601
CDR0000667954 ( Registry Identifier: NCI Physician Data Query )
No
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Principal Investigator: Asad Bashey, MD, PhD Blood and Marrow Transplant Group of Georgia
Alliance for Clinical Trials in Oncology
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP