Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas
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| ClinicalTrials.gov Identifier: NCT02228512 |
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Recruitment Status :
Withdrawn
First Posted : August 29, 2014
Last Update Posted : August 31, 2018
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Background:
- The chemotherapy combination DA-EPOCH-RP includes the drugs etoposide (E), prednisone (P), vincristine (O), cyclophosphamide (C), doxorubicin (H), rituximab (R), and pomalidomide (P). Researchers want to see if including pomalidomide will help people with two rare lymphomas.
Objectives:
- To study the safety and efficacy of the chemotherapy drugs DA-EPOCH-RP.
Eligibility:
- Adults at least 18 years old. They must have primary effusion lymphoma or large cell lymphoma arising from Kaposi sarcoma Herpesvirus-associated multicentric Castleman disease.
Design:
- Participants will be with screened with blood tests, scans, spinal tap, and bone marrow sample. They may have skin or lymph node samples taken and fluid removed from around some organs.
- Participants will have breathing and eye tests. A camera may take pictures inside their body.
- Participants will take pomalidomide alone by mouth for up to 21 days. Then they will get rituximab by intravenous (IV) catheter, which is a small tube that goes into a vein..
- Participants will have an IV inserted in an arm or chest vein to get the IV chemotherapy drugs, at the same time the will take pomalidomide by mouth for 5 days.
- They will get DA-EPOCH-RP in 21-day cycles. Most people will have 6 cycles.
- They will get 4 study drugs by IV for 5 days and 2 others by mouth for 5 days.
- They will get daily filgrastim injections in the skin until white blood counts are acceptable
- For 2 days of some cycles, methotrexate will be injected into the spinal fluid.
- After completing EPOCH-RP, some participants who have Kaposi sarcoma will be prescribed pomalidomide for 3-weeks, followed by a one week break, for up to 12 months.
- Participants will repeat the blood tests often. They will also have repeated medical history, physical exam, urine and stool tests, and pictures of any rashes associated with these lymphomas.
- Participants will have several follow-up visits over 4 years.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Large Cell Lymphoma Arising in KSHV-associated Multicentric Castleman Disease Primary Effusion Lymphoma | Drug: Pomalidomide Drug: Rituximab Drug: Prednisone Drug: Etoposide Drug: Doxorubicin Drug: Vincristine Drug: Cyclophosphamide | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 0 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase I/II Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas (Primary Effusion Lymphoma and Large Cell Lymphoma Arising in KSHV-Associated Multicentric Castleman Disease) |
| Study Start Date : | August 15, 2014 |
| Actual Primary Completion Date : | May 5, 2015 |
| Actual Study Completion Date : | May 5, 2015 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: 1
Treatment naive PEL (main cohort)
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Drug: Pomalidomide
Part A: 5 mg po daily for 21 days (full course) Part A: 5 mg po daily for 4 days (short course) Part B: 5 mg po daily for 5 days (Phase I/II dose) Part C: Phase I/II dose) po daily Day 1-21 of 28 day cycle for up to 12 cycles. Drug: Rituximab Part A: 375 mg/m2 day 22 (full course) Part A: 375 mg/m2 day 5 (short course) Part A: 375 mg/m2 day 1 (omit pomalidomode) Part B: 375 mg/m2 day 1 Drug: Prednisone Part B: 60 mg/m2/day po x 5 days (day 1-5 Drug: Etoposide Part B: 50 mg/m2/day CIVI over 24 hrs x 4 days Drug: Doxorubicin Part B: 10 mg/m2/day CIVI over 24 hrs x 4 days Drug: Vincristine Part B: 0.4 mg/m2/day CIVI over 24 hrs x 4 days Drug: Cyclophosphamide Part B: 750 mg/m2 Day 5 |
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Active Comparator: 2
Treatment na(SqrRoot) ve large cell lymphoma arising in KSHV-MCD
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Drug: Pomalidomide
Part A: 5 mg po daily for 21 days (full course) Part A: 5 mg po daily for 4 days (short course) Part B: 5 mg po daily for 5 days (Phase I/II dose) Part C: Phase I/II dose) po daily Day 1-21 of 28 day cycle for up to 12 cycles. Drug: Rituximab Part A: 375 mg/m2 day 22 (full course) Part A: 375 mg/m2 day 5 (short course) Part A: 375 mg/m2 day 1 (omit pomalidomode) Part B: 375 mg/m2 day 1 Drug: Prednisone Part B: 60 mg/m2/day po x 5 days (day 1-5 Drug: Etoposide Part B: 50 mg/m2/day CIVI over 24 hrs x 4 days Drug: Doxorubicin Part B: 10 mg/m2/day CIVI over 24 hrs x 4 days Drug: Vincristine Part B: 0.4 mg/m2/day CIVI over 24 hrs x 4 days Drug: Cyclophosphamide Part B: 750 mg/m2 Day 5 |
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Active Comparator: 3
Previously treated KSHV-NHL
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Drug: Pomalidomide
Part A: 5 mg po daily for 21 days (full course) Part A: 5 mg po daily for 4 days (short course) Part B: 5 mg po daily for 5 days (Phase I/II dose) Part C: Phase I/II dose) po daily Day 1-21 of 28 day cycle for up to 12 cycles. Drug: Rituximab Part A: 375 mg/m2 day 22 (full course) Part A: 375 mg/m2 day 5 (short course) Part A: 375 mg/m2 day 1 (omit pomalidomode) Part B: 375 mg/m2 day 1 Drug: Prednisone Part B: 60 mg/m2/day po x 5 days (day 1-5 Drug: Etoposide Part B: 50 mg/m2/day CIVI over 24 hrs x 4 days Drug: Doxorubicin Part B: 10 mg/m2/day CIVI over 24 hrs x 4 days Drug: Vincristine Part B: 0.4 mg/m2/day CIVI over 24 hrs x 4 days Drug: Cyclophosphamide Part B: 750 mg/m2 Day 5 |
- (Phase I) To determine the maximum tolerated dose and/or recommended phase II dose of pomalidomide in combination with DA-EPOCH-R. [ Time Frame: one-year ]
- (Phase II) Evaluate overall survival in treatment naive patients with primary effusion lymphoma treated with pomalidomide in combination with modified DA-EPOCH-RP [ Time Frame: one-year ]
- Evaluate response rates and progression free survival [ Time Frame: one-year ]
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
- INCLUSION CRITERIA:
2.1.1.1 KSHV-associated non-Hodgkin lymphoma, with pathology reviewed and confirmed at the NIH. May include WHO recognized tumors
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2.1.1.1.1 Primary effusion lymphoma (PEL), including extracavitary variant
2.1.1.1.2 Large cell lymphoma arising in the setting of KSHV-associated MCD.
2.1.1.2 Measurable or assessable lymphoma
2.1.1.3 Any HIV status
2.1.1.4 Age 18 years or greater. Because no dosing or adverse event data are currently available on the use of pomalidomide in combination with EPOCH-R in patients <18 years of age, children are excluded from this study, but may be eligible for future pediatric trials.
2.1.1.5 ECOG performance status 0-4.
2.1.1.6 Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 14 days prior to and again within 24 hours before starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control
2.1.1.7 All study participants must agree to be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program.
2.1.1.8 Able to take aspirin 81mg orally daily or if intolerant of aspirin, able to take a substitute thromboprophylaxis such as low molecular weight heparin.
2.1.1.9 Ability of subject to understand and the willingness to sign a written informed consent document.
EXCLUSION CRITERIA:
2.1.2.1 Use of other systemic anticancer treatments or agents within the past 2 weeks (4 weeks if the therapy was a monoclonal antibody)
2.1.2.2 Prior dose-adjusted EPOCH or pomalidomide for treatment of KSHV-associated lymphoma
2.1.2.3 Parenchymal brain involvement with lymphoma
2.1.2.4 History of malignant tumors other than KS or KSHV-associated MCD, unless: In complete remission for greater than or equal to 1 year from the time response was first documented or
- Completely resected basal cell carcinoma or
- In situ squamous cell carcinoma of the cervix or anus
2.1.2.5 Inadequate renal function, defined as calculated or estimated creatinine clearance < 60 mL/min unless lymphoma related
2.1.2.6 Inadequate hepatic function:
--2.1.2.6.1 Bilirubin (total) > 1.5 times the upper limit of normal; AST and/or ALT > 3 times the upper limit of normal; EXCEPTIONS:
- Total bilirubin greater than or equal to 5 mg/dL in patients with Gilbert's syndrome as defined by >80% unconjugated
- Total bilirubin greater than or equal to 7.5 with direct fraction > 0.7 if patient is receiving a protease inhibitor at the time of initial evaluation
- Hepatic dysfunction attributed to lymphoma
2.1.2.7 ANC <1000/mm3 and platelets < 75,000/mm3 unless lymphoma, KSHV-MCD, or KICS- related.
2.1.2.8 CTCAEv4.0 Grade 3-4 neuropathy
2.1.2.9 Ejection fraction less than 40% by echocardiography
2.1.2.10 Known drug-related, inherited, or acquired procoagulant disorder including prothrombin gene mutation 20210, antithrombin III deficiency, protein C deficiency, protein S deficiency and antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden mutation or the presence of a lupus anticoagulant in the absence of other criteria for the antiphospholipid syndrome.
2.1.2.11 History of hypersensitivity reactions attributed to thalidomide, lenalidomide, or pomalidomide, including prior development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, or pomalidomide.
2.1.2.12 Breast feeding (if lactating, must agree not to breast feed while taking pomalidomide). Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Pomalidomide, breastfeeding should be discontinued if the mother is treated with Pomalidomide.
2.1.2.13 Uncontrolled severe intercurrent illness including, but not limited to: bacterial, fungal, or life-threatening viral infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements.
2.1.2.14 Any condition, including laboratory abnormalities, which in the opinion of the Principal Investigator or Lead Associate Investigator, would prohibit administration of planned chemotherapeutic intervention, places the subject at unacceptable risk if they were to participate in the study or confounds the ability to interpret data from the study
2.1.2.15 Pregnant women are excluded from this study because pomalidomide is a Category X agent with the potential for teratogenic or abortifacient effects. These potential risks may also apply to other agents used in this study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02228512
| Principal Investigator: | Thomas S Uldrick, M.D. | National Cancer Institute (NCI) |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT02228512 |
| Other Study ID Numbers: |
140176 14-C-0176 |
| First Posted: | August 29, 2014 Key Record Dates |
| Last Update Posted: | August 31, 2018 |
| Last Verified: | May 5, 2015 |
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HHV8 PEL Immune Modulation CC-4047 IMiD |
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Lymphoma Lymphoma, Primary Effusion Castleman Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Lymphoma, B-Cell Prednisone Cyclophosphamide Rituximab Doxorubicin |
Etoposide Vincristine Pomalidomide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors |