Know Cancer

or
forgot password

Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation


Phase 2
N/A
69 Years
Open (Enrolling)
Both
Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Thank you

Trial Information

Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival (EFS)

Safety Issue:

No

Principal Investigator

Asad Bashey, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Blood and Marrow Transplant Group of Georgia

Authority:

United States: Federal Government

Study ID:

CDR0000667954

NCT ID:

NCT01118013

Start Date:

December 2010

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorder
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • 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
  • recurrent small lymphocytic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • childhood diffuse large cell lymphoma
  • childhood grade III lymphomatoid granulomatosis
  • childhood immunoblastic large cell lymphoma
  • childhood nasal type extranodal NK/T-cell lymphoma
  • post-transplant lymphoproliferative disorder
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • childhood myelodysplastic syndromes
  • recurrent childhood anaplastic large cell lymphoma
  • adult acute myelomonocytic leukemia (M4)
  • childhood acute myelomonocytic leukemia (M4)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloblastic leukemia without maturation (M1)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • adult acute promyelocytic leukemia (M3)
  • childhood acute promyelocytic leukemia (M3)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • childhood acute monoblastic leukemia (M5a)
  • childhood acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • childhood acute erythroleukemia (M6)
  • adult acute megakaryoblastic leukemia (M7)
  • childhood acute megakaryocytic leukemia (M7)
  • childhood Burkitt lymphoma
  • atypical chronic myeloid leukemia, BCR-ABL1 negative
  • chronic myelomonocytic leukemia
  • cutaneous B-cell non-Hodgkin lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • myelodysplastic/myeloproliferative neoplasm, unclassifiable
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoproliferative Disorders
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Union Hospital of Cecil CountyElkton MD, Maryland  21921