Mantle Cell LymphomaPhase 2NCT00005780
Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma
A Phase 2 study testing EPOCH-R, GM-CSF and Idiotype vaccine in people with Mantle Cell Lymphoma and Lymphoma, Mantle Cell, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This study will evaluate the safety and effectiveness of an experimental cancer vaccine for mantle cell lymphoma a form of cancer of the white blood cells called lymphocytes. Although standard treatments for lymphoma may achieve disease remission, none provides a cure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mantle Cell Lymphoma, Lymphoma, Mantle Cell
- What is being tested?
- EPOCH-R, GM-CSF and Idiotype vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2000to 16 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Tissue diagnosis of mantle cell lymphoma (confirmed in Laboratory of Pathology). Blastic cell variant will be eligible.
- Age greater than or equal to 18.
- Previously untreated with cytotoxic chemotherapy. Patients may have received local radiation or a short course of steroids for control of symptoms.
- All stages of disease.
- Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microliters of circulating tumor cells in the blood.
- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 3.
Show all 9Show fewer
- Adequate major organ function (serum creatinine 1.5 mg/dl or creatinine clearance greater than 60 ml/min; bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated; absolute neutrophil count (ANC) greater than 1000 and platelets greater than 100,000) unless impairment due to organ involvement by lymphoma.
- No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If multigated acquisition (MUGA) scan is obtained, the left ventricular ejection fraction (LVEF) should exceed 40%.
- Ability to give informed consent.
Who cannot join
- Antibodies to human immunodeficiency virus (HIV) or presence of hepatitis B surface antigen.
- Pregnant or lactating.
- Prior malignancy in past 5 years except squamous or basal cell carcinoma or curatively treated in situ of the cervix.
- Involvement of central nervous system by lymphoma.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma
This study will evaluate the safety and effectiveness of an experimental cancer vaccine for mantle cell lymphoma a form of cancer of the white blood cells called lymphocytes. Although standard treatments for lymphoma may achieve disease remission, none provides a cure.
Patients with mantle cell lymphoma 18 years and older who have not been treated previously with chemotherapy may participate in this study. Candidates will be screened for eligibility with a medical history and physical examination. Other tests that may be required include blood and urine tests; lung function studies; imaging tests such as magnetic resonance imaging, computed tomography and X-rays; and biopsy (surgical removal of a small tissue sample) of tumor, bone marrow, or other tissue.
Read more
Patients enrolled in the study will begin treatment with chemotherapy designed to reduce disease to a minimum that is, to achieve remission or shrink the tumor as much as possible. Chemotherapy will be administered on an outpatient basis over a period of around 12 to 18 weeks in 3-week cycles as follows: prednisone by mouth on days 1 through 5; etoposide, doxorubicin and vincristine intravenously through (a vein) on days 1 through 5; and cyclophosphamide intravenously on day 5. Starting day 6, patients receive no chemotherapy for 16 days. In addition, an antibody called rituximab, which attaches to lymphoma cells and may increase the effectiveness of the chemotherapy, will be given on day 1 of the cycle. Patients will also receive a protein called granulocyte colony-stimulating factor (G-CSF) starting day 6 of the cycle and continuing until the white blood cell count recovers or until day 19. G-CSF is naturally produced by bone marrow and may boost the immune system. The chemotherapy drugs and rituximab are infused through a vein by means of a lightweight portable pump, which patients are taught how to use. Patients are also how taught how to give themselves G-CSF injections under the skin, similar to insulin injections.
The first vaccination will be given at least 3 months after chemotherapy ends and will be repeated every 4 weeks for a maximum of 5 vaccinations. The vaccinations will be given in the clinic. Patients will also receive daily injections of granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth factor naturally produced by bone marrow that can boost the immune system. These injections will be given the day of the vaccination and for the next 3 days.
When vaccine therapy is completed, patients who were treated successfully will be followed with periodic clinic visits for follow-up examinations and tests. Patients in whom the lymphoma did not disappear entirely or who have a recurrence of disease will be advised of further treatment possibilities....
Read the detailed description
Background:
- Mantle cell lymphoma presents a particular clinical challenge because it is aggressive and incurable with chemotherapy. Thus, novel treatment approaches are needed.
- In follicular center cell lymphomas, another incurable disease, recent evidence suggests that molecular complete remissions may be achieved following idiotype vaccination in patients who have achieved minimal residual disease with combination chemotherapy.
- These results suggest that idiotype vaccines may be able to induce a clinically significant immune response against lymphoma.
Objectives:
- To assess if etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R)/idiotype vaccination is associated with a median progression-free survival consistent with 36 months;
- To assess if rituximab affects generation of T-cell immunity against the idiotype.
- To compare T-cell immunity using two different methods of isolating the idiotype protein.
Eligibility:
- Tissue diagnosis of mantle cell lymphoma.
- Age greater than or equal to 18 years.
- Previously untreated with cytotoxic chemotherapy. All stages of disease.
- Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microl of circulating tumor cells in the blood.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3.
Design:
- In the present study, we propose to investigate the efficacy of idiotype vaccine treatment in previously untreated patients with mantle cell lymphomas. In order to achieve minimal residual disease, patients will receive 6 cycles EPOCH chemotherapy and rituximab (EPOCH-R) followed by 5 idiotype vaccine injections.
- This study has completed accrual of 26 patients and study is closed as of 4/18/2022.
- Conditions
- Mantle Cell Lymphoma, Lymphoma, Mantle Cell
- Being tested
- EPOCH-R, GM-CSF, Idiotype vaccine
- Keywords
- Lymphoma Vaccines, Immune Response Against Lymphoma, Molecular Complete Remissions, Novel Treatment Approach, Mantle Cell Lymphoma
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPOCH-RDrug
Also called Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab
EPOCH-R for 6 cycles
GM-CSFBiological
Also called Sargramostim
Granulocyte-macrophage colony-stimulating factor (GM-CSF) monthly with the vaccine for 5 doses
Idiotype vaccineBiological
1 injection of vaccine monthly for 5 doses
| Study group | Role | What they receive |
|---|---|---|
| Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab | Experimental | Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) followed by idiotype vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF). Receives: Drug: EPOCH-R; Biological: GM-CSF; Biological: Idiotype vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
PFS is time from on study date until disease relapse or progression, death, or date of last follow-up. Progression was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma and is defined as ≥50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously involved node or the appearance of any new lesion.
Measured: From participants on study date until date of disease relapse or progression, death, or date of last follow-up, assessed up to 245.8 months
Percentage of Participants With an Antibody Response to Idiotype Vaccine
Participants with an immune response to idiotype vaccine measured by enzyme-linked immunosorbent assay (ELISA) to detect antibody binding to tumor cells. Positive response was defined as at least a fourfold increase in antibody titer.
Measured: Weeks 12 to 32
Secondary outcomes (7)
Percentage of Participants Whose Cancer Shrinks or Disappears After Treatment With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
Response was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma. Complete Response (CR) is a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., Lactate dehydrogenase (LDH) definitely assignable to the lymphoma. Complete Response Unconfirmed (CRu) is as per CR criteria except that if a residual node is > 1.5cm, it must have regressed by > 75% in the sum of the products of the greatest diameters (SPD). Partial Response (PR) is ≥50% decreased in the SPD of 6 largest dominant nodes or nodal masses. Stable Disease (SD) is defined as less than a PR but not progressive disease. Progression is ≥50% increase from nadir in the SPD of any previously involved node or the appearance of any new lesion.
Measured: After 6 cycles of EPOCH-R therapy, an average of 18 weeks
Percentage of Participants With Grade 3 or Higher Serious and/or Non-serious Toxicity That Occurred That is at Least Possibly Related to Drug or Vaccine
Serious and/or non-serious adverse events were assessed by the Common Toxicity Criteria (CTC v2.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Measured: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Overall Survival (OS)
OS was determined by the Kaplan-Meier method and is defined as the time from treatment start date until date of death or last follow-up.
Measured: Time from treatment start date until date of death or date last follow-up, up to 250 months
Progression Free Survival (PFS) in Participants Who Received Idiotype Vaccine
PFS is defined as the time from start of treatment until disease relapse or progression, death, or last follow-up. Progression was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma and is defined as ≥50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously involved node or the appearance of any new lesion
Measured: Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months
Percentage of Participants With Antibodies to Keyhole Limpet Haemocyanin (KLH)
Participants with an immune response against carrier molecule KLH measured by enzyme-linked immunosorbent assay (ELISA) to detect antibody binding to tumor cells. Positive response was defined as at least a fourfold increase in antibody titer.
Measured: After vaccinations administered at 0, 1, 2, 3 and 5 months
Percentage of Participants With Induction of Type 1 Cytokine T-cell Response
Participants with tumor specific T-cell responses during B-cell recovery was assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab and were measured by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT). A positive response required the response to be at least twice the negative controls.
Measured: After vaccinations administered at 0, 1, 2, 3 and 5 months
Time to Recovery of CD4 T Lymphocytes (CD4+)
Recovery of CD4+ was measured by flow cytometry. Blood samples were collected via apheresis and analyzed by multicolor flow cytometry in peripheral blood mononuclear cells (PBMCs) for cluster of differentiation 4 (CD4). Time to recovery of CD4 T lymphocytes was defined as the time required for CD4 T lymphocytes to increase above the lower limit of normal of the normal laboratory value range of 359 cells/mcL
Measured: After chemotherapy before vaccination, up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2000 (estimated)
- Study start1 Jun 2000
- Primary completion9 Jun 2021
- Study completion16 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Christopher Melani, MD, National Cancer Institute (NCI)
- Investigators
- Christopher J Melani, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005780
- Sponsor's protocol ID
- 000133
- Other IDs
- 00-C-0133
- Status last verified
- Jan 2023
- First submitted
- 3 Jun 2000
- Last updated
- 31 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pittaluga S, Bijnens L, Teodorovic I, Hagenbeek A, Meerwaldt JH, Somers R, Thomas J, Noordijk EM, De Wolf-Peeters C. Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation. Blood. 1996 May 15;87(10):4358-67.
PubMed 8639796Armitage JO. Management of mantle cell lymphoma. Oncology (Williston Park). 1998 Oct;12(10 Suppl 8):49-55.
PubMed 9830633Weisenburger DD, Armitage JO. Mantle cell lymphoma-- an entity comes of age. Blood. 1996 Jun 1;87(11):4483-94. No abstract available.
PubMed 8639814Grant C, Neelapu SS, MD2, Kwak LW, Dunleavy K, White T, Miller BW, Jaffe ES, Steinberg SM, Healey Bird B, MB, Wilson WH. Eleven-Year Follow-up of Idiotype Vaccine and DA-EPOCH-Rituximab in Untreated Mantle Cell Lymphoma: Correlation of Survival with Idiotype Immune Response. Blood (ASH Annual Meeting Abstracts) 2011 118: Abstract 2707.
Neelapu SS, Kwak LW, Kobrin CB, Reynolds CW, Janik JE, Dunleavy K, White T, Harvey L, Pennington R, Stetler-Stevenson M, Jaffe ES, Steinberg SM, Gress R, Hakim F, Wilson WH. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med. 2005 Sep;11(9):986-91. doi: 10.1038/nm1290. Epub 2005 Aug 21.
PubMed 16116429Roschewski M, Dunleavy K, Neelapu SS, Pittaluga S, Melani CJ, Jaffe ES, Shovlin M, Crossley B, Kong K, Jacob A, Kwak L, Wilson WH. Quantitative Baseline Circulating Tumor DNA Levels Correlate with GM-CSF Response to Idiotype Vaccine in Untreated Mantle Cell Lymphoma (ASH Annual Meeting Abstracts). Blood. 2016;128:2943-2943.
Wilson WH, Neelapu S, White T, et al: Idiotype Vaccine Following EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma. Pro Am Soc Heme, 2002.
Neelapu S, Wilson WH, Baskar W, et at: Induction of T-cell responses by tumor antigen vaccination in mantle cell lymphoma following rituximab-based treatment. Pro Am Soc Clin Oncol, 2003.
Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003 Feb;3(2):185-97. doi: 10.1016/s1535-6108(03)00028-x.
PubMed 12620412Wilson WH, Neelapu S, Rosenwald A, et al: Idiotype Vaccine and Dose-Adjusted EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma: Preliminary Report on Clinical Outcome and Analysis of Immune Response. 2003, Blood 102 (11) #358.
Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Muller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC; Lymphoma/Leukemia Molecular Profiling Project. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood. 2005 Dec 15;106(13):4315-21. doi: 10.1182/blood-2005-04-1753. Epub 2005 Aug 25.
PubMed 16123218Wiestner A, Tehrani M, Chiorazzi M, Wright G, Gibellini F, Nakayama K, Liu H, Rosenwald A, Muller-Hermelink HK, Ott G, Chan WC, Greiner TC, Weisenburger DD, Vose J, Armitage JO, Gascoyne RD, Connors JM, Campo E, Montserrat E, Bosch F, Smeland EB, Kvaloy S, Holte H, Delabie J, Fisher RI, Grogan TM, Miller TP, Wilson WH, Jaffe ES, Staudt LM. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood. 2007 Jun 1;109(11):4599-606. doi: 10.1182/blood-2006-08-039859. Epub 2007 Feb 13.
PubMed 17299095Dunleavy K, Neelapu SS, Kwak LW, Grant C, Santos CF, Popa M, White T, Miller B, Jaffe ES, Steinberg SM and Wilson WH. Association of idiotype vaccine-induced T-cell response with improved survival and time-to-next treatment (TTNT) in untreated mantle cell lymphoma (MCL). Journal of Clinical Oncology, 2012 ASCO Annual Meeting Proceedings (Post-Meeting Edition).Vol 30, No 15_suppl (May 20 Supplement), 2012: 2528.
Lai C, Cole DE, Steinberg SM, Lucas N, Dombi E, Melani C, Roschewski M, Balis F, Widemann BC, Wilson WH. Doxorubicin pharmacokinetics and toxicity in patients with aggressive lymphoma and hepatic impairment. Blood Adv. 2023 Feb 28;7(4):529-532. doi: 10.1182/bloodadvances.2022007431.
PubMed 35882475
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Idiotype Vaccine and EPOCH-Rituximab Chemotherapy in Untreated Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00005780
- Acronym / sponsor ID
- 000133
- Conditions
- Mantle Cell Lymphoma, Lymphoma, Mantle Cell
- Keywords
- Lymphoma Vaccines, Immune Response Against Lymphoma, Molecular Complete Remissions, Novel Treatment Approach, Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 1 Jun 2000 (actual)
- Primary completion
- 9 Jun 2021 (actual)
- Study completion
- 16 Jun 2021 (actual)
- First posted
- 5 Jun 2000 (estimated)
- Results
- Posted 31 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of an experimental cancer vaccine for mantle cell lymphoma a form of cancer of the white blood cells called lymphocytes. Although standard treatments for lymphoma may achieve disease remission, none provides a cure.
Patients with mantle cell lymphoma 18 years and older who have not been treated previously with chemotherapy may participate in this study. Candidates will be screened for eligibility with a medical history and physical examination. Other tests that may be required include blood and urine tests; lung function studies; imaging tests such as magnetic resonance imaging, computed tomography and X-rays; and biopsy (surgical removal of a small tissue sample) of tumor, bone marrow, or other tissue.
Patients enrolled in the study will begin treatment with chemotherapy designed to reduce disease to a minimum that is, to achieve remission or shrink the tumor as much as possible. Chemotherapy will be administered on an outpatient basis over a period of around 12 to 18 weeks in 3-week cycles as follows: prednisone by mouth on days 1 through 5; etoposide, doxorubicin and vincristine intravenously through (a vein) on days 1 through 5; and cyclophosphamide intravenously on day 5. Starting day 6, patients receive no chemotherapy for 16 days. In addition, an antibody called rituximab, which attaches to lymphoma cells and may increase the effectiveness of the chemotherapy, will be given on day 1 of the cycle. Patients will also receive a protein called granulocyte colony-stimulating factor (G-CSF) starting day 6 of the cycle and continuing until the white blood cell count recovers or until day 19. G-CSF is naturally produced by bone marrow and may boost the immune system. The chemotherapy drugs and rituximab are infused through a vein by means of a lightweight portable pump, which patients are taught how to use. Patients are also how taught how to give themselves G-CSF injections under the skin, similar to insulin injections.
The first vaccination will be given at least 3 months after chemotherapy ends and will be repeated every 4 weeks for a maximum of 5 vaccinations. The vaccinations will be given in the clinic. Patients will also receive daily injections of granulocyte-macrophage colony-stimulating factor (GM-CSF), a growth factor naturally produced by bone marrow that can boost the immune system. These injections will be given the day of the vaccination and for the next 3 days.
When vaccine therapy is completed, patients who were treated successfully will be followed with periodic clinic visits for follow-up examinations and tests. Patients in whom the lymphoma did not disappear entirely or who have a recurrence of disease will be advised of further treatment possibilities....
Detailed description
Background:
- Mantle cell lymphoma presents a particular clinical challenge because it is aggressive and incurable with chemotherapy. Thus, novel treatment approaches are needed.
- In follicular center cell lymphomas, another incurable disease, recent evidence suggests that molecular complete remissions may be achieved following idiotype vaccination in patients who have achieved minimal residual disease with combination chemotherapy.
- These results suggest that idiotype vaccines may be able to induce a clinically significant immune response against lymphoma.
Objectives:
- To assess if etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R)/idiotype vaccination is associated with a median progression-free survival consistent with 36 months;
- To assess if rituximab affects generation of T-cell immunity against the idiotype.
- To compare T-cell immunity using two different methods of isolating the idiotype protein.
Eligibility:
- Tissue diagnosis of mantle cell lymphoma.
- Age greater than or equal to 18 years.
- Previously untreated with cytotoxic chemotherapy. All stages of disease.
- Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microl of circulating tumor cells in the blood.
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3.
Design:
- In the present study, we propose to investigate the efficacy of idiotype vaccine treatment in previously untreated patients with mantle cell lymphomas. In order to achieve minimal residual disease, patients will receive 6 cycles EPOCH chemotherapy and rituximab (EPOCH-R) followed by 5 idiotype vaccine injections.
- This study has completed accrual of 26 patients and study is closed as of 4/18/2022.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab | Experimental | Drug: EPOCH-R, Biological: GM-CSF, Biological: Idiotype vaccineEtoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) followed by idiotype vaccine and granulocyte-macrophage colony-stimulating factor (GM-CSF). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Tissue diagnosis of mantle cell lymphoma (confirmed in Laboratory of Pathology). Blastic cell variant will be eligible.
- Age greater than or equal to 18.
- Previously untreated with cytotoxic chemotherapy. Patients may have received local radiation or a short course of steroids for control of symptoms.
- All stages of disease.
- Lymph node of greater than or equal to 2 cm accessible for biopsy/harvest or greater than 1000/microliters of circulating tumor cells in the blood.
Key exclusion criteria (4 listed)
- Antibodies to human immunodeficiency virus (HIV) or presence of hepatitis B surface antigen.
- Pregnant or lactating.
- Prior malignancy in past 5 years except squamous or basal cell carcinoma or curatively treated in situ of the cervix.
- Involvement of central nervous system by lymphoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EPOCH-RAlso: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximabEPOCH-R for 6 cycles | Drug | Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab |
| GM-CSFAlso: SargramostimGranulocyte-macrophage colony-stimulating factor (GM-CSF) monthly with the vaccine for 5 doses | Biological | Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab |
| Idiotype vaccine1 injection of vaccine monthly for 5 doses | Biological | Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab |
Primary outcome
Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
Time frame: From participants on study date until date of disease relapse or progression, death, or date of last follow-up, assessed up to 245.8 months
PFS is time from on study date until disease relapse or progression, death, or date of last follow-up. Progression was measured by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphoma and is defined as ≥50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously involved node or the appearance of any new lesion.
Percentage of Participants With an Antibody Response to Idiotype Vaccine
Time frame: Weeks 12 to 32
Participants with an immune response to idiotype vaccine measured by enzyme-linked immunosorbent assay (ELISA) to detect antibody binding to tumor cells. Positive response was defined as at least a fourfold increase in antibody titer.
7 secondary outcomes
Percentage of Participants Whose Cancer Shrinks or Disappears After Treatment With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R)
Time frame: After 6 cycles of EPOCH-R therapy, an average of 18 weeks
Percentage of Participants With Grade 3 or Higher Serious and/or Non-serious Toxicity That Occurred That is at Least Possibly Related to Drug or Vaccine
Time frame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years
Overall Survival (OS)
Time frame: Time from treatment start date until date of death or date last follow-up, up to 250 months
Progression Free Survival (PFS) in Participants Who Received Idiotype Vaccine
Time frame: Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months
Percentage of Participants With Antibodies to Keyhole Limpet Haemocyanin (KLH)
Time frame: After vaccinations administered at 0, 1, 2, 3 and 5 months
Percentage of Participants With Induction of Type 1 Cytokine T-cell Response
Time frame: After vaccinations administered at 0, 1, 2, 3 and 5 months
Time to Recovery of CD4 T Lymphocytes (CD4+)
Time frame: After chemotherapy before vaccination, up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8639796Pittaluga S, Bijnens L, Teodorovic I, Hagenbeek A, Meerwaldt JH, Somers R, Thomas J, Noordijk EM, De Wolf-Peeters C. Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation. Blood. 1996 May 15;87(10):4358-67.
- Background: PubMed 9830633Armitage JO. Management of mantle cell lymphoma. Oncology (Williston Park). 1998 Oct;12(10 Suppl 8):49-55.
- Background: PubMed 8639814Weisenburger DD, Armitage JO. Mantle cell lymphoma-- an entity comes of age. Blood. 1996 Jun 1;87(11):4483-94. No abstract available.
- Results publicationGrant C, Neelapu SS, MD2, Kwak LW, Dunleavy K, White T, Miller BW, Jaffe ES, Steinberg SM, Healey Bird B, MB, Wilson WH. Eleven-Year Follow-up of Idiotype Vaccine and DA-EPOCH-Rituximab in Untreated Mantle Cell Lymphoma: Correlation of Survival with Idiotype Immune Response. Blood (ASH Annual Meeting Abstracts) 2011 118: Abstract 2707.
- Results publication: PubMed 16116429Neelapu SS, Kwak LW, Kobrin CB, Reynolds CW, Janik JE, Dunleavy K, White T, Harvey L, Pennington R, Stetler-Stevenson M, Jaffe ES, Steinberg SM, Gress R, Hakim F, Wilson WH. Vaccine-induced tumor-specific immunity despite severe B-cell depletion in mantle cell lymphoma. Nat Med. 2005 Sep;11(9):986-91. doi: 10.1038/nm1290. Epub 2005 Aug 21.
- Results publicationRoschewski M, Dunleavy K, Neelapu SS, Pittaluga S, Melani CJ, Jaffe ES, Shovlin M, Crossley B, Kong K, Jacob A, Kwak L, Wilson WH. Quantitative Baseline Circulating Tumor DNA Levels Correlate with GM-CSF Response to Idiotype Vaccine in Untreated Mantle Cell Lymphoma (ASH Annual Meeting Abstracts). Blood. 2016;128:2943-2943.
- Results publicationWilson WH, Neelapu S, White T, et al: Idiotype Vaccine Following EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma. Pro Am Soc Heme, 2002.
- Results publicationNeelapu S, Wilson WH, Baskar W, et at: Induction of T-cell responses by tumor antigen vaccination in mantle cell lymphoma following rituximab-based treatment. Pro Am Soc Clin Oncol, 2003.
- Results publication: PubMed 12620412Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003 Feb;3(2):185-97. doi: 10.1016/s1535-6108(03)00028-x.
- Results publicationWilson WH, Neelapu S, Rosenwald A, et al: Idiotype Vaccine and Dose-Adjusted EPOCH-Rituximab Treatment in Untreated Mantle Cell Lymphoma: Preliminary Report on Clinical Outcome and Analysis of Immune Response. 2003, Blood 102 (11) #358.
- Results publication: PubMed 16123218Fu K, Weisenburger DD, Greiner TC, Dave S, Wright G, Rosenwald A, Chiorazzi M, Iqbal J, Gesk S, Siebert R, De Jong D, Jaffe ES, Wilson WH, Delabie J, Ott G, Dave BJ, Sanger WG, Smith LM, Rimsza L, Braziel RM, Muller-Hermelink HK, Campo E, Gascoyne RD, Staudt LM, Chan WC; Lymphoma/Leukemia Molecular Profiling Project. Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood. 2005 Dec 15;106(13):4315-21. doi: 10.1182/blood-2005-04-1753. Epub 2005 Aug 25.
- Results publication: PubMed 17299095Wiestner A, Tehrani M, Chiorazzi M, Wright G, Gibellini F, Nakayama K, Liu H, Rosenwald A, Muller-Hermelink HK, Ott G, Chan WC, Greiner TC, Weisenburger DD, Vose J, Armitage JO, Gascoyne RD, Connors JM, Campo E, Montserrat E, Bosch F, Smeland EB, Kvaloy S, Holte H, Delabie J, Fisher RI, Grogan TM, Miller TP, Wilson WH, Jaffe ES, Staudt LM. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood. 2007 Jun 1;109(11):4599-606. doi: 10.1182/blood-2006-08-039859. Epub 2007 Feb 13.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Mantle Cell Lymphoma
Not yet recruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Glofitamab, to the Usual Chemotherapy Treatment (Alternating R-CHOP/R-DHAP) for Previously Untreated Mantle Cell Lymphoma
Ann Arbor Stage II Mantle Cell Lymphoma, Ann Arbor Stage III Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma
Lymphoma
RecruitingPhase 1
A Study of LY4152199 in Participants With Previously Treated B-cell Malignancies (BAF_FRontier-1 )
Lymphoma, Non-Hodgkin, B-cell Lymphoma
RecruitingPhase 2
Auto Stem Cell Transplant for Lymphoma Patients
Non-Hodgkin Lymphoma, Hodgkin Lymphoma
Active, not recruitingPhase 1
Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
Hematologic Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher J Melani, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EPOCH-R, GM-CSF and Idiotype vaccine in people with Mantle Cell Lymphoma and Lymphoma, Mantle Cell, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R) (time frame: From participants on study date until date of disease relapse or progression, death, or date of last follow-up, assessed up to 245.8 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005780, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2023.