Name, Sponsor, Eligibility
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Untreated patients with Stage III/IV follicular lymphoma (follicular small
cleaved cell, follicular mixed cell or follicular large cell) diagnosed within 24 months
of screening. No prior or concurrent primary CNS Lymphoma. Patients must have accessible
tumor for biopsy.
Recruiting nearly 400 patients.
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Phase 3 Randomized Trial to
Evaluate the Safety and Efficacy of the Specific Immunotherapy Compared to Non-specific
Immunotherapy, KLH with GM-CSF, in Patients with Follicular Non-Hodgkin¹s Lymphoma
(Double-blinded) Vaccine description:
Recombinant Idiotype Conjugated to KLH. (RNA based type.)
Pretreatment: All patients receive CVP
(cytoxan, vincristine, prednisone)
Cyclophosphamide is 1000 mg/m2 in 500 cc of D5W given IV over 30-40 minutes on day 1 of treatment,
Vincristine is 1.4 mg/m2 IV push on Day 1,
Prednisone is 100 mg orally on Days 1-5.
The body surface area is the m2 calculation. It is based on the patient's height and weight.
NOTE: For Genitope's study, the doses above are recommended. However, some references cite the CVP dose of cyclophosphamide as 800-1000 mg/m2. Most indicate that 2 mg of vincristine is the maximum dose that should be administered at each treatment. And some references also cite the prednisone dose as 60 mg/m2 and many use a 3-5 day taper (gradually decreasing dose over the 3-5 day period). For Genitope's study a prednisone taper can be used. It is up to the oncologist and usually a decision based on how the patient tolerates stopping the steroid without a taper.
Required pretreatment response: After
pretreatment, if you receive a CR (complete response) or PR (Partial Response?), you will
be randomly assigned to receive the Id vaccine or to receive KLH alone. Each group
receives GM-CSF immune system booster. After
Chemotherapy Comparisons of NCI and Genitope Protocols
NCI
Beginning 6-12 months after completion of chemotherapy, patients who achieve
CR or CRu are randomized to 1 of 2 treatment arms.
Genitope:
At 6 months after completion of chemotherapy, patients maintaining partial
response (PR), complete response (CR), or unconfirmed complete response
(CRU) receive immunotherapy. Patients are stratified according to
participating center and baseline disease status (PR vs CR/CRU).
Patients are randomized to one of two treatment arms. |
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Untreated Stage III or IV follicular lymphoma. Patients must have an accessible
grape-sized lymph node (2 cm). Patients also must have no lymphoma in the central nervous
system or brain.
Recruiting ~563 patients, about 375 are expected to be eligible to
receive vaccine
after chemotherapy. A patient has a 2/3 chance of getting vaccine if a
satisfactory response to chemotherapy is achieved. Thus about 250 patients will
receive vaccine and 313 won't.
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Phase 3 Randomized Trial of
Patient-Specific Vaccination with Conjugated Follicular Lymphoma-Derived Idiotype with
Local GM-CSF in First Complete Remission Vaccine
description: Idiotype Protein conjugated to KLH. (Fusion rescue type.)
Pretreatment: All patients receive PACE
(prednisone, adriamycin, cytoxan and etoposide)
Required pretreatment response: If
pretreatment results in a CR (complete response), you will be randomly assigned to receive
a vaccine called Id/KLH or to receive KLH alone. Each group receives GM-CSF an immune
system booster. After
Chemotherapy Comparisons of NCI and Genitope Protocols
NCI
Beginning 6-12 months after completion of chemotherapy, patients who
achieve CR or CRu are randomized to 1 of 2 treatment arms.
Genitope:
At 6 months after completion of chemotherapy, patients maintaining partial
response (PR), complete response (CR), or unconfirmed complete response
(CRU) receive immunotherapy. Patients are stratified according to
participating center and baseline disease status (PR vs CR/CRU).
Patients are randomized to one of two treatment arms. |
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Previously treated patients With Low-Grade or Follicular B-Cell Non-Hodgkin's
Lymphoma Histologically confirmed low-grade or follicular B-cell non-Hodgkin's lymphoma
Small lymphocytic Follicular small cleaved cell Follicular mixed cell Follicular large
cell At least 1 bidimensional lesion measuring 2 cm in each dimension Tumor accessible for
biopsy
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Phase II Study of Autologous Tumor
Cell Vaccine With Adjuvant Sargramostim (GM-CSF) (Summary Last Modified 04/2001) Vaccine description: Autologous Tumor Cell Vaccine vaccine
coupled to keyhole limpet hemocyanin and sargramostim (GM-CSF) subcutaneously (SC) on day
1 and GM-CSF SC on days 2-4 of months 1-4 and 6.
Required pretreatment response: NA.
Responded with at least stable disease to most recent chemotherapy or rituximab therapy
for a minimum of 90 days and currently relapsed or stable disease
Exclusion Criteria: No greater than 4
relapses following prior chemotherapy or rituximab therapy No known CNS lymphoma or
meningeal lymphomatosis
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Histologically confirmed mantle cell lymphoma Blastic cell variant allowed All
stages of disease Chemotherapy naive Lymph node at least 2 cm accessible for
biopsy/harvest OR Greater than 1,000/mm3 of circulating tumor cells in the blood No CNS
involvement by lymphoma
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Phase II Pilot Study of Etoposide,
Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R) Followed
By Immunotherapy With Autologous Tumor-Derived Immunoglobulin Idiotype Conjugated to
Keyhole Limpet Hemocyanin Plus Sargramostim (GM-CSF) in Patients With Previously Untreated
Mantle Cell Lymphoma (Summary Last Modified 02/2001) Vaccine description: Autologous Tumor-Derived Immunoglobulin
Idiotype Conjugated to Keyhole Limpet Hemocyanin Plus Sargramostim (GM-CSF)
Required pretreatment response: None
specified |
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Pt with previously treated or untreated* follicular center cell
grade I/II lymphoma, small, MALT, monocytoid B-cell lymphoma, Waldenstrom's
macroglobulinemia, or marginal zone lymphoma with bidimensionally measurable disease.
* Dr. Younes indicated that the protocol has changed to allow untreated
patients. Patients can also pretreat with Rituxan. However, if pretreatment with Rituxan,
the tumor sample must be taken after the Rituxan treatment.
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A Phase II Trial Of Active Specific
Immunotherapy In Patients With Indolent Lymphoma Using Autologous Lymphoma-Derived Heat
Shock Protein-Peptide Complex Vaccine
description: Autologous Lymphoma-Derived Heat Shock Protein-Peptide Complex Link to Details
Pretreatment: None (Perhaps Rituxan for
untreated patients in near future)
Required pretreatment response: NA. Pt must
have no chemo, immunotherapy, radiotherapy or experimental anti-cancer therapy within 6
wks prior to starting HSPPC-96 administration.
Exclusion Criteria: Pts: with active or
prior history of central nervous system lymphoma; serious intercurrent medical illnesses,
requiring hospitalization; history of primary or 2ndary immunodeficiency (other than
related to mal. lymphoma because treatment is dependent on functional immune system) or
pts taking immunosuppressive drugs, i.e. systemic corticosteroids; who are pregnant or
lactating; receiving growth factors of any kind, including G-CSF, GM-CSF, or Epogen; with
bulky disease, defined as greater than 10cm in diameter; with more than 4 previous
treatment regimens. |
VACCINE STUDY
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PROS-
FACT: The Genitope Vaccine produced immune
responses in 13/16 (81%) of patients with advanced follicular lymphoma who
had no other treatment at all.
FACT: The Genitope Vaccine produced patient specific
immune responses in 13/21 case of people treated with CVP and having at
least partial remissions in a Phase II trial.
FACT: Genitope produced vaccine 143 times of 143
cases.
FACT: Genitope makes vaccine for everyone in the
Phase III trial, even if they are in the control group.
FACT: The required pretreatment for the phase III
trial produces eligibility for vaccine 75% of the time. The overall
chance of getting vaccine for a patient submitting to a biopsy is 50%.
CONJECTURE: Long term significance of an immune
response to the Genitope vaccine will be the same as for the NCI vaccine.
CONJECTURE: The Genitope vaccine may be cheaper and
faster to make.
CONJECTURE: The Genitope process by intent is supposed
to capture variations missed by the NCI vaccine. Whether it does and
whether it turns out to work for patients will take years to determine.
CONJECTURE: The institutions working with Genitope on
Phase II and Phase III trials are the best in the world...they wouldn't
undertake a new vaccine given the results of the NCI phase II trial
without good reason.
CONS-
FACT: There are no published, peer reviewed studies of
the Genitope vaccine or the clinical trials done with it so far. All
public data is from conferences.
FACT: There is no public data to indicate that Genitope
has produced vaccines that are more comprehensive in covering variant Id
than the NCI style vaccine.
FACT: There is no data showing any clinical
benefit to any individual or patient group treated with this vaccine.
It is too early for such data to be available.
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PROS-
FACT: 17 of 20 patients are still in remission going on
7-8 years. <Kwak's paper, in your site already, and conversation with
Vivian, I think.>
FACT: 19 of 20 patients had some kind of response to the
vaccine. This group of 20 patients had a complete response or
complete response unconfirmed to prior chemotherapy, unlike other trials
where partials responders also were given vaccine and included in the
statistics.
FACT: the vaccine was shown to have caused a tumor
specific response for each of 6 patients tested by some very comprehensive
and elaborate tests.
FACT: The same vaccine, with a different adjuvant also
has produced long term remissions in 18 of 20 patients who responded, but
only 20 of 40 patients responded- probably due to the adjuvant choice at
the time. 100% of a study group of 14 are alive 10+ years after
vaccination. (Stanford, Levy)
CONS-
FACT: The vaccine is expensive and difficult to make
compared to other options. The claimed failure rate is 10-15%.
FACT: There required pretreatment for the NCI
phase III trial only qualifies 66 some percent of the patients.
Overall, only 42% of the people submitting to biopsy will receive vaccine.
FACT: NCI does not make vaccine for patients in
the control group.
CONJECTURE: It is possible for the vaccine to target
only a small fraction of the tumor. The vaccine is made by fusion of
tumor cells with mouse cells. Only one fusion cell will be picked but more
frequent idiotypes will have a better chance of being picked. This
is a rare possibility, especially in view of trial results.
CONJECTURE: There are variations in the target Id immunoglobulin. Some of
these variations may not be captured by the NCI vaccine because of the way
it is made. The vaccine won't teach the body to attack cells with those
variations. Hence the cancer may reoccur. A new vaccine could be made when
this happens. Again this will be extremely rare as both Genitope and NCI
vaccines are polyclonal (several epitopes are targeted even if only one
idiotype was cloned). Therefore, most of the variants (although
theoretically some may not) will be targeted in both vaccines. |
SKCC-2001
Favrille (FavId-01)
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PROS-
FACT: Closest alternative to Genitope Vaccine
FACT: It's the only available trial that's open
to previously treated patients. It requires no pretreatment with chemotherapy.
FACT: Phase II study that's open to pts with
stable or progression grade 1 or 2 follicular b-cell lymphoma
FACT: Known success with GM-CSF
FACT: Unlimited amounts of vaccine can be created once the
Idiotype protein is successfully cloned. Future re-administration of vaccine, as
needed, seems more likely with this group.
CONS-
Fact: Made using fruit fly cells instead of mouse
(Genitope) or mouse-human hybrid (NCI)
FACT: One patient (no 4) died from what appears to be
transformation of disease to high grade while under treatment. Liver
complications resulted due to the presence of the transformed lymphoma in
the liver.
FACT: New group at this, background unclear
CONJECTURE: preliminary word of mouth that first 3 are
showing tumor regression. Also word of mouth that one of those three
has dropped out due to progression. |
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PROS-
FACT: Uses whole cell membrane, not just idiotype protein
FACT: Associated with experienced vaccine group
FACT: They seem willing to answer questions too.
CONS-
FACT: Phase I
FACT: No published data supporting this approach
CONJECTURE you may get too small a dose to matter
CONJECTURE-Less known about IL-2 in this context.
CONJECTURE- may not have enough just because they use tumor
sample itself, they don't grow extra copies just in case. |
- General Information &
Abstracts -
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Tumor-specific
proteins are isolated from the patient's biopsied tissue. Then various strategies are used
to create a vaccine that "educates" the patient's immune system to identify
those proteins as foreign and attack the tumors.
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