Kaposi sarcoma (KS) is a cancer most often seen in people with HIV. It causes lesions. These
are usually on the skin but sometimes in the lymph nodes, lungs, and gastrointestinal tract.
Researchers think a combination of drugs may help treat KS.
To test a combination of the anti-cancer drugs pomalidomide (CC-4047) and liposomal
doxorubicin (Doxil) in people with KS.
People ages 18 and over with KS
Participants will be screened with:
Blood, urine, and heart tests
Biopsy: A small sample of tissue is taken from a KS lesion.
Possible CT scan
Possible exam of lungs or gastrointestinal tract with an endoscope: A flexible instrument
inside the organ.
Participants will take the drugs in 4-week cycles. They will take Doxil through an IV on Day
1 of each cycle. They will take CC-4047 tablets by mouth each day for the first 3 weeks of
Participants will have many visits:
Before starting treatment
To start each cycle
Day 15 of first 2 cycles
Visits include repeats of screening tests and:
Multiple blood draws
Photographs of lesions
Participants will keep a drug diary.
Participants will take aspirin or other drugs to prevent blood clots.
Participants with HIV will have combination antiretroviral therapy.
Some participants will have a PET scan.
Participants will continue treatment as long as they tolerate it and their KS improves. After
treatment, they will have several follow-up visits for up to 5 years
Kaposi Sarcoma (KS) is a multicentric angioproliferative tumor that most frequently
involves skin, but can also involve lymph nodes, lungs and gastrointestinal tract. It is
most common in people with HIV or other forms of immune compromise. Patients with
AIDS-associated KS have worse survival than HIV-infected patients without KS.
Patients may present with advanced disease KS and/or concurrent KSHV-associated
multicentric Castleman disease (MCD) or an IL-6 related KSHV-associated cytokine
syndrome (KICS). Patients with the latter conditions have poor outcomes when treated
with FDA-approved cytotoxic therapies used for KS, and novel approaches are needed.
A Phase I/II Study demonstrated that pomalidomide 5 mg daily on days 1- 21 of a 28 Day
Cycle was safe and tolerable in patients with KS with or without HIV. Increased CD4+ and
CD8+ T-cell counts and KS regression were observed.
Combination of pomalidomide with liposomal doxorubicin may offer a new approach for
patients with advanced KS or KS and concurrent KSHV-associated MCD or KICS
Evaluate the safety and tolerability of various dose combinations of pomalidomide and
liposomal doxorubicin in two groups of patients: Group I) KS requiring systemic therapy;
Group II) KS with concurrent KSHV-associated MCD or KICS
To assess the pharmacokinetics (PK) of pomalidomide in combination with liposomal
doxorubicin; and for patients with HIV in combination with antiretroviral therapy
To preliminarily evaluate the antitumor effect of pomalidomide in combination with
liposomal doxorubicin against Kaposi sarcoma.
Patients with biopsy proven (confirmed in the Laboratory of Pathology, CCR) Kaposi
Group I: KS requiring systemic therapy (no prior therapy required)
T1 KS, KS on skin sufficiently widespread that it is not amenable to local therapy,
or KS affecting quality of life due to local symptoms or psychological distress
--KS patients with an inadequate response to pomalidomide (either progressive disease or
stable disease after 4 months)
KS patients with an inadequate response to liposomal doxorubicin, paclitaxel, or other
systemic chemotherapy (either progressive disease or stable disease after 6 cycles)
Group I will exclude patients eligible for Group II (below).
A wash out period off treatment of 3 weeks will be required, except in the case of
patients with progressive, severe disease in which delay of treatment cannot be
justified (i.e. symptomatic pulmonary KS)
-Group II: KS in one of the following high-risk groups (no prior therapy required):
KSHV Inflammatory Cytokine Syndrome (KICS), including those also meeting clinical
criteria for KS immune reconstitution syndrome (KS IRIS)
Patients with primary effusion lymphoma or a large cell lymphoma arising in
KSHV-associated MCD are excluded.
At least five measurable cutaneous KS lesions with no previous local
radiation, surgical or intralesional cytotoxic therapy that would prevent
response assessment for that lesion; or other evaluable disease.
ECOG Performance Status (PS): Group I: less than or equal to 2, Group II: less
than or equal to 3, ECOG PS of 4 (with Karnofsky 20%) will be allowed in Group
II only if symptoms due to pulmonary KS.
Measurable disease by the criteria proposed by the AIDS Clinical Trials Group
Oncology Committee (for KS).
Patient or legal guardian must be willing to give informed consent.
Patients can be HIV positive or negative.
HAART for HIV+ patients.
This is a Phase I study evaluating 2 groups of patients with KS. Patients will receive
pomalidomide once a day, days 1-21 of a 28-day cycle, at the various dose levels
combined with liposomal doxorubicin IV day 1 of a 28-day cycle until optimal tumor
response, unacceptable toxicity, or patient request to discontinue
Patients with HIV will be prescribed HAART.
All patients will receive thromboprophylaxis, generally with aspirin 81 mg tablet
The study will proceed to an antitumor activity phase to assess in a preliminary manner
the response of Group I patients to a fixed dose of pomalidomide and liposomal
doxorubicin. Up to 30 subjects (HIV positive or negative) evaluable for response will be
treated at the highest tolerable combination of pomalidomide and liposomal doxorubicin
(determined to be dose level 3: pomalidomide 4mg in combination with 20mg/m^2 liposomal
doxorubicin) to gain preliminary information on antitumor activity in an expansion
cohort. Based on the observation of positive results in the initial dose expansion of 14
patients evaluated in the expansion cohort, a total of 30 patients will be allowed to be
included in this cohort in order to gain additional safety information as well as to
improve the precision of the estimate of the response rate in Group I patients.
The study will also include an antitumor activity phase to assess in a preliminary
manner the response of Group II patients to a fixed dose of pomalidomide and liposomal
doxorubicin. Up to 10 total patients (HIV positive or negative) evaluable for response
will be treated at the highest tolerated dose of pomalidomide for this population
(determined to be dose level, 2mg in combination with 20mg/m2 liposomal doxorubicin) to
gain preliminary information on KS that occurs concurrently with KSHV-MCD or KICS.
This study will also evaluate the characteristics of 18fluoro-thymidine (FLT) positron
emission tomography (PET) in patients with KS and concurrent KSHV-associated MCD or
KICS, and correlate with markers of KSHV-lytic activation.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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