Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00006486

Trial Description

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Title

Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-center Trial

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This clinical trial studies fludarabine phosphate, low-dose total body irradiation, and
donor stem cell transplant in treating patients with hematologic malignancies or kidney
cancer. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation
before a donor 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. The
donated stem cells may replace the patient's immune cells 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 cyclosporine before the transplant and cyclosporine and mycophenolate mofetil
after the transplant may stop this from happening.

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Brief Summary in Scientific Language

PRIMARY OBJECTIVES:

I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell
donors can be safely established using a non-myeloablative conditioning regimen in patients
with hematologic malignancies and renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with
mixed or full donor chimerism to eliminate persistent or progressive disease.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4
to -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone
marrow transplantation on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to
100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day
96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of
graft-versus-host disease and who have been off immunosuppression for at least 2 weeks
undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

After completion of study treatment, patients are follow-up periodically for 5 years.

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Organizational Data

  •   DRKS00006486
  •   2015/03/24
  •   2000/06/02
  •   yes
  •   [---]*
  •   [---]*
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Secondary IDs

  •   NCT00005799  (ClinicalTrials.gov)
  •   1463.00  (Fred Hutchinson Cancer Research Center)
  •   NCI-2012-00667 
  •   1463.00 
  •   P30CA015704 
  •   P01CA018029 
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Health Condition or Problem studied

  •   Accelerated Phase Chronic Myelogenous Leukemia
  •   Adult Acute Lymphoblastic Leukemia in Remission
  •   Adult Acute Myeloid Leukemia in Remission
  •   Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  •   Adult Acute Myeloid Leukemia With Del(5q)
  •   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)
  •   B-cell Chronic Lymphocytic Leukemia
  •   Childhood Acute Lymphoblastic Leukemia in Remission
  •   Childhood Acute Myeloid Leukemia in Remission
  •   Childhood Chronic Myelogenous Leukemia
  •   Childhood Myelodysplastic Syndromes
  •   Childhood Renal Cell Carcinoma
  •   Chronic Phase Chronic Myelogenous Leukemia
  •   Clear Cell Renal Cell Carcinoma
  •   de Novo Myelodysplastic Syndromes
  •   Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  •   Nodal Marginal Zone B-cell Lymphoma
  •   Previously Treated Myelodysplastic Syndromes
  •   Recurrent Adult Acute Lymphoblastic Leukemia
  •   Recurrent Adult Acute Myeloid Leukemia
  •   Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  •   Recurrent Adult Hodgkin Lymphoma
  •   Recurrent Childhood Acute Lymphoblastic Leukemia
  •   Recurrent Childhood Acute Myeloid Leukemia
  •   Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  •   Recurrent Grade 1 Follicular Lymphoma
  •   Recurrent Grade 2 Follicular Lymphoma
  •   Recurrent Marginal Zone Lymphoma
  •   Recurrent Mycosis Fungoides/Sezary Syndrome
  •   Recurrent Small Lymphocytic Lymphoma
  •   Recurrent/Refractory Childhood Hodgkin Lymphoma
  •   Refractory Chronic Lymphocytic Leukemia
  •   Refractory Hairy Cell Leukemia
  •   Refractory Multiple Myeloma
  •   Relapsing Chronic Myelogenous Leukemia
  •   Splenic Marginal Zone Lymphoma
  •   Stage III Renal Cell Cancer
  •   Stage IV Renal Cell Cancer
  •   T-cell Large Granular Lymphocyte Leukemia
  •   Type 1 Papillary Renal Cell Carcinoma
  •   Type 2 Papillary Renal Cell Carcinoma
  •   Waldenström Macroglobulinemia
  •   C64 -  Malignant neoplasm of kidney, except renal pelvis
  •   C81-C96 -  Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue
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Interventions/Observational Groups

  •   Drug: fludarabine phosphate
  •   Radiation: total-body irradiation
  •   Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  •   Procedure: allogeneic bone marrow transplantation
  •   Procedure: peripheral blood stem cell transplantation
  •   Biological: therapeutic allogeneic lymphocytes
  •   Drug: cyclosporine
  •   Drug: mycophenolate mofetil
  •   Other: pharmacological study
  •   Other: laboratory biomarker analysis
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Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   N/A
  •   [---]*
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Primary Outcome

- Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism; time frame: At day 56; Engraftment will be assessed separately among patients who receive bone marrow and patients who receive PBSC. Patients with low-risk and high-risk disease will be assessed separately.

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Secondary Outcome

- Disease-free survival; time frame: Up to 200 days; Will be summarized.
- Relapse; time frame: Assessed up to 5 years; Will be summarized.
- Disease-related mortality; time frame: Before day 200; Will be summarized.
- Response of malignancy to DLI; time frame: Assessed up to 5 years; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of myelosuppression; time frame: Greater than 2 days after initial PBSC infusion; Absolute neutrophil count (ANC) less than 500/ul for more than 2 days, platelets less than 20,000/ul for more than 2 days. Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of aplasia after DLI; time frame: Greater than 2 days after initial PBSC infusion; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of grades 2-4 acute GVHD after DLI; time frame: Until day 90; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of grades 2-4 acute GVHD after PBSC infusion; time frame: Up to day 177; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of grades 2-4 chronic extensive GVHD after DLI; time frame: Assessed up to 5 years; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Dose of CD3+ required to convert mixed to full lymphoid chimeras; time frame: Day 28 post-transplant; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Dose of CD3+ required to convert mixed to full lymphoid chimeras; time frame: Day 56 post-transplant; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Dose of CD3+ required to convert mixed to full lymphoid chimeras; time frame: Day 84 post-transplant; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.
- Incidence of infections; time frame: Assessed up to 5 years; Examined and reported in a descriptive manner and confidence intervals will be presented for all estimates. Analyses will be conducted separately among the low- and high-risk groups.

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Countries of Recruitment

  •   United States
  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   1999/11/30
  •   90
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   no maximum age
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Additional Inclusion Criteria

- Age > 50 years with hematologic malignancies treatable by allogeneic hematopoietic
stem cell transplant (HSCT) and all patients with B cell malignancies except those
who may be cured by autologous stem cell transplantation (SCT)

- Age =< 50 years of age with hematologic diseases treatable by allogeneic HSCT who
through pre-existing medical conditions or prior therapy are considered to be of high
risk for regimen related toxicity associated with a conventional transplant or those
patients who refuse a conventional SCT; transplants must be approved for these
inclusion criteria by both the participating institution's patient review committee
such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research
Center [FHCRC]) and by the principal investigator

- Patients with metastatic renal cell carcinoma with the histologic subtypes of clear
cell, papillary and medullary may be accepted regardless of age

- The following diseases will be permitted although other diagnoses can be considered
if approved by PCC or the participating institution's patient review committees and
the principal investigator

- Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma
(HL) - must have received and failed frontline therapy

- Multiple myeloma - must have received prior chemotherapy; consolidation of
chemotherapy by autografting prior to nonmyeloablative HSCT is permitted

- Acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) - must be in
complete remission and have received cytotoxic chemotherapy at some stage before
transplant; patients with molecular or early relapse will be accepted providing
a donor is available; patients with persistent or refractory disease will be
considered on a case by case basis and transplants must be approved by the
institution's patient review committees

- Chronic myelogenous leukemia (CML) - patients will be accepted in chronic phase
or accelerated phase; patients who have received prior autografts after high
dose therapy or have undergone intensive chemotherapy for either peripheral
blood stem cell (PBSC) mobilization or treatment of advanced CML may be enrolled
provided they are in complete remission (CR), chronic phase (CP) or accelerated
phase (AP)

- Myelodysplastic syndromes (MDS) - all patients with MDS will be eligible for
this protocol; however, those patients with MDS and frank AML (> 30% blasts in
bone marrow aspirate by morphology or flow cytometry) will require induction
chemotherapy to obtain a complete remission (marrow blasts < 5%) and remain in
complete remission at time of transplant

- Renal cell carcinoma- must have evidence of disease not amenable to surgical
cure or metastatic disease by radiological and histological criteria

- DONOR: Human leukocyte antigen (HLA) matched unrelated donor; donors should be
matched for HLA -A, -B, -C, -developmentally regulated ribonucleic acid (RNA) binding
protein 1(DRB)1 and -class II, DQ beta 1 (DQB) 1; HLA -A and -B loci should be
matched at least to the level of resolution; HLA -C, -DRB1, and -DQB1 should be typed
at the highest level of resolution available at the time of donor selection; donor
must consent to either a bone marrow harvest or PBSC mobilization with filgrastim
(G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor
centers

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Exclusion Criteria

- Patients with rapidly progressive intermediate or high grade NHL

- Renal cell carcinoma patients with expected survival of less than 6 months

- Bulky disease resulting in severely limited performance status (< 70%)

- Any vertebral instability

- Any active central nervous system (CNS) involvement with disease

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Females who are pregnant

- Patients with non-hematological tumors

- Cardiac ejection fraction < 30%

- Diffusion capacity of the lung for carbon monoxide (DLCO) < 30% and/or receiving
supplementary continuous oxygen

- Significant elevation of bilirubin and transaminases should be discussed at
participating institutions' patient review committees in a case by case basis;
evidence of synthetic dysfunction or severe cirrhosis will result in patient
exclusion

- Karnofsky score < 50 (except renal cell carcinoma [RCC])

- Patients with poorly controlled hypertension on multiple antihypertensives

- Human immunodeficiency virus (HIV) positive patients

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Addresses

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    • Fred Hutchinson Cancer Research Center
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    •   [---]*
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    • National Heart, Lung, and Blood Institute (NHLBI)
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    •   [---]*
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    • National Cancer Institute (NCI)
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    •   [---]*
    •   [---]*
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  • start of 1:1-Block address scientific-contact
    • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Brenda Sandmaier 
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    • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Brenda Sandmaier 
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    •   [---]*
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up continuing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   3
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.