Relapsed / Refractory
Studies GROUPED
BY:
TOPIC
SEARCH Drug
Resistance and Lymphoma in ClinicalTrials.gov |
Clinical
Trials for Refractory Lymphoma
Goal: Treating the disease using investigational
therapies or new combinations of
therapies that that may overcome
drug resistance. NOTE: By definition, clinical
trials are investigational, and it is therefore
not known if the
goals of treatments will be realized.

Monoclonal Antibody
Monoclonal
antibodies are man-made antibodies
(proteins) that target receptors on lymphoma cells.
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 | New:
*
Condition:
B-cell lymphomas, including CLL
Rationale
and goal: "Drugs
used in chemotherapy, such as fenretinide, work in different ways
to stop the growth of cancer cells, either by killing the cells or
by stopping them from dividing. Monoclonal antibodies, such as
rituximab, can block cancer growth in different ways. Some find
cancer cells and kill them or carry cancer-killing substances to
them. Others interfere with the ability of cancer cells to grow
and spread. Giving fenretinide together with rituximab may kill
more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and
best dose of fenretinide and to see how well it works when given
together with rituximab in treating patients with B-cell
non-Hodgkin's lymphoma."
* Fenretinide (4-HPR) is a retinoid (vitamin A) analogue with
antitumor and chemopreventive activities. In a mouse model,
Fenretinide showed synergy with Rituxan.
TOPIC SEARCH
Mechanisms - PubMed
TOPIC SEARCH Outcome data - Medscape |
PubMed
TOPIC SEARCH
Safety or Toxicity - PubMed
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potential next generation anti-cd20 antibody
 | AME-133v
(modified anti-cd20 antibody)
Condition: Relapsed follicular lymphoma, or Refractory cd-20 positive NHL
with "low affinity form of Fc?RIIIa (F/F or F/V at position 158) as determined by FcR genotyping; "
Rationale and goal: The protein engineering of AME-133v
is hypothesized to result in an anti-CD20 therapy with greater potency and efficacy in all patients, but
particularly in genetically defined subpopulations that respond poorly to rituximab because they express a low
affinity version of the Fc receptor on their immune effector cells.
A monoclonal antibody that has
increased binding for this receptor should be more effective in stimulating effector cell killing and thus
improve response to the antibody. This study is designed to provide evidence of the safety and a preliminary
understanding of the efficacy of AME 133v..
Also see: Anti-CD20 monoclonal antibody with enhanced affinity for CD16 activates NK cells at lower
concentrations and more effectively than rituximab - bloodjournal.org
TOPIC SEARCH
Mechanisms - PubMed
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potential next generation anti-cd20 antibody
 |
Condition:
 | Relapsed or refractory follicular
lymphoma grade I-II
 | Tumor verified to be CD20 positive
 | CT scan showing demarcated lesions |
| |
Rationale and goal: The
purpose of this trial is to determine the safety and efficacy of
HuMax-CD20 as a treatment for
Follicular Lymphoma (FL).
AND:
Rationale and goal: The
purpose of this trial is to determine the safety and efficacy of
HuMax-CD20 as a treatment for
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Novel Chemotherapy Agents
Monoclonal
antibodies are man-made antibodies (proteins) that target receptors on
lymphoma cells.
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novel
chemotherapy agent - similar to anthracyclines
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Pixantrone
(BBR 2778) Versus Other Chemotherapeutic Agents
Condition: Third line Relapsed Aggressive Lymphoma, Non-Hodgkin
Rationale and
goal: BBR 2778 is a novel aza-anthracenedione that has activity
in experimental tumors and shows reduced potential for
cardiotoxicity in animal models. This cytotoxic agent has
structural similarities with mitoxantrone as well as general
similarities with anthracyclines (such as the tricyclic
central quinoid chromophore).
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Novel Targeted Agents
Drugs
that target pathways that may have high specificity to Lymphoma cells.
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 | BMS-247550
(epothilone)
Conditions: Relapsed or
Refractory Aggressive Non-Hodgkin's Lymphoma -
including
grade 3 follicular
Rationale and goal: This drug provides unique mechanisms that
may overcome drug resistance.
About BMS 247550 -
The epothilones are a new class of natural products that
induce hyperstabilization of polymerized tubulin in a fashion similar to that known for
the taxanes. Unique to these compounds is their ability to
overcome acquired drug resistance, regardless of whether it
is related to over expression of p-glycoprotein (MDR) or tubulin mutations. Given the novel mechanism, a
Phase
2 study of BMS247550 in patients with drug resistant lymphoma was undertaken. ASCO
2005
TOPIC SEARCH
Mechanisms - PubMed
TOPIC
SEARCH Outcome data - ASCO
| Medscape |
PubMed
TOPIC SEARCH
Safety or Toxicity - ASCO
| PubMed
|

combining novel
chemo and targeted agents
 |
SDX-105
(Bendamustin/Treanda™) with Bortezomib (Velcade)
Condition: Relapsed or Refractory Indolent Non-Hodgkin's
Lymphoma or B-CLL
Rationale and
goal: Bendamustin and bortezomib have been shown to be effective in
the treatment of patients with indolent Non-Hodgkin's Lymphoma
(NHL) and Chronic Lymphocytic Leukemia (CLL). Both compounds
appear not to be cross-resistant with prior therapy. Therefore,
it is of interest to combine bendamustine and bortezomib in this
patient population.
Preliminary results from patients with multiple myeloma showed
that the combination of bendamustine and bortezomib is
efficacious and well tolerated. However, there are so far no
data on this combination in patients with NHL or CLL.
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MGCD0103 Given Three Times Weekly
Condition: Relapsed or refractory DLBCL or Follicular
Lymphoma
Rationale and
goal: MGCD0103 is an experimental drug that belongs to a class
of drugs known as the histone deacetylase inhibitors, which
may restore normal control in cancer cells by affecting the
genes and proteins that are being made. Laboratory tests
show that this new investigational anti-cancer drug can slow
down the growth of human cancer cells in mice; two clinical
research studies are currently being performed in humans
with cancer and a similar study is being performed in
patients with the same disease.
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Novel Immunotherapy
Protocols
enlisting
the immune system to target Lymphoma cells.
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Intratumoral
Injection of CPG 7909, Combined With Low dose Local Radiation
NOTE: Study closed as of March 2008, might reopen
before end of year.
Condition: low-grade B-cell lymphoma of any initial
stage or mycosis fungoides of stage IB-IVA. B-cell lymphoma
patients must have failed at least one prior treatment. Mycosis
fungoides patients must have failed or have been intolerant of
at least 2 topical or one systemic treatment.
Rationale and
goal: This is a single institution
phase I / II trial to evaluate the safety, feasibility and
efficacy of CpG injections (4 intratumoral injections followed
by 6 peri-tumoral injections) combined with local irradiation in
patients with recurrent low-grade lymphomas.
Patients will receive low-dose radiotherapy to a single tumor
site on days 1 and 2 (2 Gy each day). CpG injections will be
administered into the same tumor site within the 24 hours before
and the 24 hours after the radiation, and on days 8 and 15.
Weekly doses of CpG will be then administered subcutaneously in
the region of previous injections for 6 additional doses.
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combining radiotherapy with radioimmunotherapy
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Radiation and Bexxar
Condition: Previously treated follicular
lymphoma with > 5 cm nodal tumors.
Rationale and
goal: "As the toxicity of Radiotherapy and Bexxar may not
overlap, the combination of both may allow an increase in the therapeutic window for both radiotherapy
and Bexxar therapy."
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combining
targeted agents with radioimmunotherapy
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Combined Weekly
Velcade and Bexxar
Condition: Relapsed or Refractory Follicular Lymphoma
Rationale and
goal: The purpose of this study is to determine what dose of
bortezomib in combination with tositumab I-131 is tolerable
whether bortezomib and Tositumomab I-131 are effective in
the treatment of relapsed or refractory non-hodgkin's
lymphoma (NHL). Both agents are effective in treating
relapsed and refractory NHL. Administer of the agents
together may sensitize the cells to the radiation from
Tositumomab I-131.
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utilizing
genetically altered t-cells to target lymphoma cells

utilizing
genetically altered t-cells to target lymphoma cells
 | Cellular Immunotherapy Using Autologous T Cell Cytolytic Clones Genetically Modified to be CD19-Specific and Express HyTK
Conditions: CD19 expressing -
Follicular lymphoma (grade I, II or III),
Lymphoplasmacytoid lymphoma,
Marginal zone lymphoma (splenic, nodal or extranodal),
Mantle cell lymphoma,
Small lymphocytic lymphoma (SLL) /chronic lymphocytic leukemia (CLL)
Rationale and goal: The purpose of this study is to assess the safety and
feasibility of collecting T cells (blood cells that help fight
infection) from subjects with this disease, genetically modifying
them in the laboratory to recognize this type of lymphoma cell,
and infusing them (giving them back by vein) to the same subjects.
In addition to assessing the safety of delivering
lymphoma-specific T cells, the safety of using the hormone IL-2 to
support the survival of the infused T cells will also be studied.
This study will also try to determine how long these cells stay in
the blood stream after re-infusion and if they attack lymphoma
cells once they are inside the body.
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novel immune modulating / targeted agent
 |
Lenalidomide
(Revlimid)
Condition: Relapsed or Refractory Hodgkin Disease
Rationale and goal: Lenalidomide
may stop the growth of cancer cells by blocking blood flow
to the cancer .
... evaluating the activity of Lenalidomide in
patients with relapsed or refractory Hodgkin's lymphoma.
AND:
|
 | Lenalidomide
(Revlimid)
Conditions: Refractory CLL or SLL
Rationale and goal: Lenalidomide
may stop the growth of cancer cells by blocking blood flow to the
cancer .
... is studying how well lenalidomide works in treating patients
with chronic lymphocytic leukemia or small lymphocytic lymphoma
that did not respond to treatment.
TOPIC SEARCH
Mechanisms - PubMed
TOPIC
SEARCH Outcome data - ASCO
| Medscape |
PubMed
TOPIC SEARCH
Safety or Toxicity - ASCO
| PubMed
|

combines Rituxan
with an immune modulating agent
 | Rituxan
and/or Lenalidomide (Revlimid)
Condition: follicular lymphoma - relapsed following
Rituxan-based combination therapy
Rationale and goal: Monoclonal antibodies, such as rituximab, can block cancer
growth in different ways. Some block the ability of cancer cells
to grow and spread. Others find cancer cells and help kill them or
carry cancer-killing substances to them.
Biological therapies, such as lenalidomide, may stimulate the
immune system in different ways and stop cancer cells from
growing. Lenalidomide may also stop the growth of non-Hodgkin's
lymphoma by blocking blood flow to the cancer. Giving rituximab
together with lenalidomide may kill more cancer cells.
TOPIC SEARCH: Mechanisms PubMed
Outcome ASCO
| Medscape |
PubMed
Safety ASCO
| PubMed
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combines a targeted
agent with rituxan immunotherapy
 | CCI-779 and
Rituxan
Condition: Relapsed or Refractory Mantle Cell lymphoma
Rationale and goal: CCI-779 - Single-agent CCI-779 has substantial anti-tumor activity in relapsed MCL. This study demonstrates that agents, which selectively target cellular pathways dysregulated in MCL cells can produce therapeutic benefit.
The high response rate warrants further studies of this agent in MCL, but the high incidence of hematologic toxicity suggests that a lower dose should be explored.
CCI-779 at 25mg is currently being evaluated in MCL through an NCCTG trial
Abstract #129 appears in Blood, Volume 104, issue 11, November 16, 2004
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combines
radioimmunotherapy with monoclonal antibody to treat challenging
CNS lymphoma
 |
Rituxan
and Zevalin
Condition: Recurrent primary central nervous system (CNS) lymphoma
Rationale and
goal: Monoclonal antibodies, such as rituximab and yttrium Y 90
ibritumomab tiuxetan, can locate cancer cells and either kill
them or deliver radioactive cancer-killing substances to them
without harming normal cells.
This clinical trial is studying how well giving Zevalin
together with Rituxan works in treating patients with
recurrent primary CNS lymphoma.
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combines Rituxan and
Radioimmunotherapy with an immune adjuvant
 | Rituxan
and Zevalin and Cp7909 (an immune adjuvant)
Condition: Refractory and relapsed NHL (including
transformed follicular NHL, MALT, MCL, and DLBCL)
Rationale and
goal: Biological therapies, such as
CpG 7909, may stimulate the immune system in different ways and
stop cancer cells from growing. Monoclonal antibodies, such as
Rituxan and Zevalin, can block cancer growth in different ways.
Some block the ability of cancer cells to grow and spread. Others
find cancer cells and help kill them or carry cancer-killing
substances to them. Giving CpG 7909 together with monoclonal
antibodies may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best
dose of CpG 7909 when given together with rituximab (Rituxan) and
yttrium Y 90 ibritumomab tiuxetan (Zevalin) in treating patients
with non-Hodgkin's lymphoma that is recurrent or did not respond
to previous treatment.
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combines
Radioimmunotherapy with a second agent in T-cell and Hodgkins
lymphomas
 | Yttrium-90 Radiolabeled Humanized Anti-Tac
and Calcium-DTPA
Conditions: Tac-Expressing -
Cutaneous T Cell Lymphoma;
Hodgkin's Disease;
Neoplasm;
Non Hodgkin's Lymphoma;
Peripheral T Cell Lymphoma
Rationale and goal: Monoclonal
antibodies can locate cancer cells and either kill them or deliver
cancer-killing substances to them without harming normal cells.
... is studying the side effects and best dose of radiolabeled
monoclonal antibody when given together with pentetic acid calcium
and to see how well they work in treating patients with recurrent
Hodgkin's lymphoma or non-Hodgkin's lymphoma.
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adoptive
immunotherapy in EBV-positive lymphomas
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LMP2a-Specific
Cytotoxic T-Lymphocytes Following CD45 Antibody for Lymphoma
Condition: EBV-positive Lymphoma
Rationale and
goal: To determine the safety of autologous/syngeneic or allogeneic
LMP-2 specific cytotoxic T-lymphocytes (CTL) in combination with
CD45 monoclonal antibody (Mab) in patients with EBV positive
Hodgkins disease (HD) or non Hodgkins lymphoma (NHL).
To obtain information on the expansion, persistence and
anti-tumor effects of of autologous/syngeneic or allogeneic
LMP-2 specific cytotoxic T-lymphocytes (CTL) given after
lymphodepletion with CD45 monoclonal antibody (Mab) in patients
with EBV positive Hodgkins disease or non Hodgkins lymphoma.
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Novel Chemo-immunotherapy protocols
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 | Vaccine
with Interleukin-2 After Combination Chemotherapy
Condition: Previously treated, or untreated, Mantle Cell
Lymphoma
Rationale and goal: Vaccines made from gene-modified cells and a person's
cancer cells may make the body build an effective immune response
to kill cancer cells. Interleukin-2 (IL-2) may stimulate the white
blood cells to kill cancer cells. Giving booster vaccinations may
make a stronger immune response and prevent or delay the
recurrence of cancer. Drugs used in chemotherapy work in different
ways to stop the growth of cancer cells, either by killing the
cells or by stopping them from dividing. Giving more than one drug
(combination chemotherapy) may kill more cancer cells. Giving
vaccine therapy together with IL-2 after combination chemotherapy
may be a more effective treatment for mantle cell lymphoma.
... studying how well giving vaccine therapy together with
IL-2 after combination chemotherapy works in treating patients
with relapsed or de novo stage II, stage III, or stage IV mantle
cell lymphoma
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Stem Cell Transplant (SCT)-based protocols
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utilizing cord blood
for stem cell graft
 |
Conditions
Rationale and goal: The
purpose of this study is to determine the efficacy and safety of
transplanting StemEx® in patients
with certain hematological malignancies. For these patients, it is
suggested that StemEx® can improve
upon the outcome of transplanting a single, un-manipulated cord
blood unit by significantly increasing the number of
stem/progenitor cells available to the patient..
Clinical
Need: Only 30% of patients who could benefit from
this procedure have an HLA-matched sibling. The lengthy search for
a matched donor may critically delay transplantation. In addition,
far fewer patients of racial minorities find suitable HLA-matched
donors. Umbilical cord blood (UCB) has been increasingly used as
an alternative source of stem cells; however, its use in adults
and adolescent patients is limited due to insufficient cell dose
required for satisfactory hematopoietic reconstitution.
TOPIC SEARCH Cord blood derived Stem Cell transplantation - PubMed

standard SCT with
cord blood derived cells
Umbilical
Cord Blood Transplantation
Conditions:
High risk childhood non-Hodgkin's lymphoma;
Graft Versus Host
Disease;
Leukemia;
Lymphoma;
Myelodysplastic (MDS) and
myeloproliferative diseases
Rationale and
goal: Umbilical cord blood transplantation may allow doctors to
give higher doses of chemotherapy or radiation therapy and kill
more cancer cells.
... studying allogeneic umbilical cord blood transplantation to
see how well it works when given with chemotherapy or radiation
therapy in treating patients with high-risk hematologic cancer.
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utilizing graft
versus lymphoma affect
 | SCT
Donor
Stem Cell Transplant
Conditions:
Childhood Hodgkin's lymphoma;
Childhood
non-Hodgkin's lymphoma; Leukemia;
Lymphoma; myelodysplastic
and myeloproliferative diseases - (eligible if relapse from
Auto SCT)
Rationale and goal: Giving low doses of chemotherapy, such as fludarabine
and busulfan, before a donor bone marrow or peripheral blood stem
cell transplant helps stop the growth of cancer cells. It also
stops the patient’s immune system from rejecting the donor’s
stem cells. The donated stem cells may replace the patient’s
immune system 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 immunosuppressive therapy after the transplant may
stop this from happening.
... studying how well donor bone marrow or peripheral stem cell
transplant works in treating patients with relapsed hematologic
cancer after treatment with chemotherapy and autologous stem cell
transplant.
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the goal of
treatment is to consolidate SCT with investigational vaccine
therapy
 |
Vaccine
Therapy Following Chemotherapy and Peripheral Stem Cell
Transplantation
Condition: recurrent grade 1-3 follicular lymphoma
Rationale and
goal: Vaccines made from a person's cancer cells may make the body
build an immune response to kill cancer cells. Vaccine therapy
may be an effective treatment for non-Hodgkin's lymphoma.
... to study the effectiveness of vaccine therapy following
chemotherapy and peripheral stem cell transplantation in
treating patients who have non-Hodgkin's lymphoma.
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Radioimmunotherapy
and Stem Cell Transplant
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Radioimmunotherapy as
part of conditioning for Stem Cell Transplantation
Related
Outcome Report: Radioimmunotherapy with 131-I tositumomab
(Bexxar) enhanced survival in good prognosis relapsed and
high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving
high-dose chemotherapy and autologous stem cell
transplantation. ASCO
2007
Conclusions: The addition of 131-I tositumomab to BEAM
and autologous stem cell transplant for relapsed or high-risk
chemosensitive DLBCL produces a 3-yr OS of 81% without excess
toxicity. This compares favorably to historical controls. This
regimen is currently being tested in a phase III trial in the BMT/CTN
of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with
relapsed chemosensitive DLBCL.
 | Rituxan/BEAM
versus Bexxar/BEAM with Autologous Stem Cell Transplantation
Conditions: Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-Cell
NHL
Rationale and goal: "The 0401 study addresses the issue of the best high-dose therapy regimen to use in a group of patients for whom autologous [harvested cells from self] transplantation is accepted as the treatment
of choice – those with diffuse large cell lymphoma failing front-line therapy (either not achieving remission
or relapsing). The major cause of treatment failure after autotransplants in this situation is lymphoma recurrence.
This study examine whether replacing Rituxan with and radiaoactive compound, Bexxar
(which also targets CD20 cells) will decrease the relapse rate without increasing toxicity. "
also see protocol/0401
AND:
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 | Bexxar
followed by BEAM conditioning study and Autologous Stem Cell
Transplant
Conditions: Relapsed Diffuse Large B-cell Lymphoma
Rationale and
goal: Monoclonal antibodies can locate cancer cells and either kill
them or deliver cancer-killing substances to them without harming
normal cells. Drugs used in chemotherapy use different ways to
stop cancer cells from dividing so they stop growing or die.
Combining chemotherapy with peripheral stem cell transplant may
allow the doctor to give higher doses of chemotherapy drugs and
kill more cancer cells.
... studying how well monoclonal antibody therapy, chemotherapy,
and peripheral stem cell transplant work in treating patients with
relapsed or refractory non-Hodgkin's lymphoma.
AND:
|
 |
Conditions:
Rationale and
goal: The purpose of this study is to
assess the safety of 131I-anti-B1 Radioimmunotherapy when combined
with high-dose BEAM or BEAC chemotherapy and hematopoietic stem
cell transplantation. The study will also compare the difference
in response rates and time to treatment failure between historical
control patients receiving high-dose BEAM or BEAC chemotherapy
with autologous hematopoietic stem cell transplant and patients
receiving radioimmunotherapy and high-dose BEAM or BEAC
chemotherapy with autologous hematopoietic stem cell transplant.
Patients will receive escalating doses of radioimmunotherapy with
anti-B1 radiolabeled with 131Iodine, high-dose carmustine,
etoposide, cytarabine and Melphalan (BEAM) chemotherapy, and
autologous hematopoietic stem cell transplant.
AND:
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 | Bexxar,
Etoposide, and Cyclophosphamide Followed by Autologous Stem Cell Transplantation
Conditions: Relapsed or Refractory non-Hodgkin's lymphoma
Rationale and goal: Radiolabeled monoclonal antibodies, such as Bexxar, can locate
cancer cells and deliver radioactive cancer-killing substances to
them without harming normal cells. Drugs used in chemotherapy,
such as etoposide and cyclophosphamide, use different ways to stop
cancer cells from dividing so they stop growing or die. Combining
a radiolabeled monoclonal antibody with combination chemotherapy
before autologous stem cell transplantation may kill more cancer
cells.
... to study the effectiveness of combining Bexxar with etoposide
and cyclophosphamide followed by autologous stem cell
transplantation in treating patients who have relapsed or
refractory non-Hodgkin's lymphoma.
AND:
|
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Bexxar Followed by Autologous Stem Cell
Transplantation
Condition: Older patients with relapsed or refractory NHL
Rationale and
goal: Radiolabeled monoclonal antibodies, such as Bexxar, can locate
cancer cells and deliver radioactive cancer-killing substances
to them without harming normal cells. Drugs used in
chemotherapy, such as etoposide and cyclophosphamide, use
different ways to stop cancer cells from dividing so they stop
growing or die. Combining a radiolabeled monoclonal antibody
with combination chemotherapy before autologous stem cell
transplantation may kill more cancer cells.
... to study the effectiveness of combining iodine I 131
tositumomab with etoposide and cyclophosphamide followed by
autologous stem cell transplantation in treating patients who
have relapsed or refractory non-Hodgkin's lymphoma.
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