Know Cancer

or
forgot password

Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors


Phase 2
N/A
75 Years
Not Enrolling
Both
Myeloproliferative Disorders, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Thank you

Trial Information

Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors


OBJECTIVES:

- To assess the percentage of patients with hematological malignancies or renal cell
carcinoma who achieve > 90% donor T-cell chimerism at 30 days after treatment with
reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose
cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral
blood progenitor cell transplantation from a matched related donor.

- To assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
and extensive chronic GVHD in these patients.

- To assess whether this regimen is associated with reduced transplant-related toxicity
and increased tolerability in these patients.

- To assess the overall safety of this conditioning regimen as measured by 6-month
transplant-related mortality in these patients.

- To determine the efficacy of this regimen in inducing durable remissions in these
patients.

OUTLINE:

- Reduced-intensity conditioning (RIC): Patients receive anti-thymocyte globulin IV over
4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate IV over 30
minutes on days -7 to -3, busulfan IV over 3 hours on days -4 and -3, and
cyclophosphamide IV over 1-2 hours on day -2.

- Transplantation: Patients undergo allogeneic peripheral blood progenitor cell
transplantation on day 0.

- Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus every 12
hours on days -1 to 90, followed by a taper until day 150. Patients also receive
methotrexate IV on days 1, 3, and 6.

Blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte
globulin and PCR analysis for chimerism.

After completion of study therapy, patients are followed periodically for up to 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of one of the following:

- Chronic myeloid leukemia (CML)

- Philadelphia chromosome (Ph)- and/or BCR-ABL-positive disease

- In chronic or accelerated phase

- Suboptimal response to imatinib mesylate (i.e., no hematologic complete
response by 3 months, no major cytogenetic response by 6 months, or no
complete cytogenetic response by 1 year)

- CML in blastic transformation allowed provided patient achieved complete
remission (CR) or second chronic phase after treatment with imatinib
mesylate or chemotherapy

- Chronic lymphocytic leukemia meeting one of the following criteria:

- Rai stage III or IV disease

- Rai stage I or II disease that failed standard therapy (i.e., disease is
progressing after ≥ 1 course of standard therapy)

- Non-Hodgkin lymphoma (NHL) meeting one of the following criteria:

- Indolent NHL

- Clinical stage III or IV disease or bulky stage II disease (i.e., ≥
one lymphoid mass > 5 cm in ≥ one dimension)

- Relapsed after primary therapy OR is refractory to therapy

- Aggressive NHL

- Is not considered curable with standard chemotherapy or autologous
stem cell transplantation (i.e., relapsed after autologous stem cell
transplantation)

- Chemotherapy-responsive disease

- Multiple myeloma

- Durie-Salmon stage II or III disease

- Durie Salmon stage I disease allowed provided β2 microglobulin level >
3 mg/dL

- Acute myeloid leukemia or acute lymphocytic leukemia

- In CR (defined as < 5% blasts in bone marrow and no circulating blasts) AND
has any of the following poor prognostic features:

- WBC > 100,000/mm^3 at presentation

- In second or greater remission

- Adverse-risk cytogenetics (i.e., Ph1-positive, 11q23 translocation,
-5, -7, complex translocations, or other recognized adverse-risk
cytogenetics)

- Renal cell carcinoma

- Stage IV disease

- Clear cell morphology

- Myelodysplastic syndromes

- Bone marrow blasts ≤ 10% on last bone marrow biopsy prior to
transplantation

- Myeloproliferative disease

- Anticipated life expectancy on conventional therapy < 10 years

- No uncomplicated essential thrombocythemia or primary polycythemia

- Hodgkin lymphoma

- Relapsed after ≥ 1 standard-dose chemotherapy regimen

- Not considered curable by autologous stem cell transplantation

- No clinical evidence of active CNS involvement

- Previously treated leptomeningeal disease allowed provided CSF cytology is
negative at the time of assessment for transplantation

- Available 6/6 allele match (i.e., HLA-A, B, DRβ1)matched related donor

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Bilirubin < 3 times normal (unless abnormality due to malignancy)

- AST and ALT < 3 times normal (unless abnormality due to malignancy)

- Creatinine ≤ 2.0 mg/dL

- LVEF ≥ 40% by MUGA or ECHO

- DLCO ≥ 40% of predicted

- FEV-1 ≥ 50% of predicted

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Deemed to be an appropriate candidate for allogeneic SCT

- No evidence of myocardial infarction within the past 6 months

- No psychological or social condition that may interfere with study participation

- No serious uncontrolled localized or active systemic infection

- No second malignancy within the past 3 years except for completely excised
nonmelanotic skin cancer or in situ carcinoma of the cervix

- No chronic inflammatory disorder requiring the continued use of glucocorticoids or
other immunosuppressive medications

- No known HIV positivity

- No hypersensitivity to E. coli-derived proteins

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation

Outcome Description:

Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.

Outcome Time Frame:

Day 30

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: Food and Drug Administration

Study ID:

CDR0000618483

NCT ID:

NCT00787761

Start Date:

April 2007

Completion Date:

May 2012

Related Keywords:

  • Myeloproliferative Disorders
  • Kidney Cancer
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • accelerated phase CML
  • blastic phase CML
  • Philadelphia chromosome positive CML
  • stage I CLL
  • stage II CLL
  • stage III CLL
  • stage IV CLL
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • adult AML with 11q23 (MLL) abnormalities
  • adult CML in remission
  • adult ALL in remission
  • stage IV renal cell cancer
  • de novo MDS
  • previously treated MDS
  • secondary MDS
  • atypical CML, BCR-ABL negative
  • chronic myelomonocytic leukemia
  • MDS/myeloproliferative neoplasm, unclassifiable
  • primary myelofibrosis
  • chronic neutrophilic leukemia
  • recurrent adult Hodgkin lymphoma
  • clear cell renal cell carcinoma
  • adult AML with inv(16)(p13;q22)
  • adult AML with t(15;17)(q22;q12)
  • adult AML with t(16;16)(p13;q22)
  • adult AML with t(8;21)(q22;q22)
  • adult nasal type extranodal NK/T-cell lymphoma
  • AML/transient myeloproliferative disorder
  • Burkitt lymphoma
  • chronic phase CML
  • extranodal marginal zone B-cell lymphoma of mucosa tissue
  • nodal marginal zone B-cell lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • contiguous st II adult diffuse small cleaved cell lymphoma
  • noncontiguous st II diffuse small cleaved cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • contiguous stage II marginal zone lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • recurrent marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • splenic marginal zone lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent adult T-cell leukemia/lymphoma
  • stage III adult T-cell leukemia/lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • Neoplasms
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601