NCT00005780

Chemotherapy Plus Vaccination to Treat Mantle Cell Lymphoma

Completed Phase 2 Results posted Last updated 31 January 2023

What this trial tests

Phase 2 trial testing EPOCH-R in Mantle Cell Lymphoma in 26 participants. Completed in 16 June 2021.

Timeline

1 June 2000

Primary endpoint
9 June 2021

16 June 2021

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	26
Start date	1 June 2000
Primary completion	9 June 2021
Estimated completion	16 June 2021
Sites	1 location across United States

Drugs / interventions tested

• EPOCH-R — full drug profile →
• GM-CSF (gm-csf) — full drug profile →
• Idiotype vaccine — full drug profile →

Conditions studied

• Mantle Cell Lymphoma — all drugs for Mantle Cell Lymphoma →
• Lymphoma, Mantle Cell — all drugs for Lymphoma, Mantle Cell →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Mantle Cell Lymphoma or Lymphoma, Mantle Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Median Progression-free Survival (PFS) in Participants Treated With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R) Primary · 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.

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	23.5	8.8 – 245.8

Percentage of Participants With an Antibody Response to Idiotype Vaccine Primary · 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.

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	30

Percentage of Participants Whose Cancer Shrinks or Disappears After Treatment With Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab (EPOCH-R) Secondary · After 6 cycles of EPOCH-R therapy, an average of 18 weeks

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

Complete Response

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	80.8

Complete Response Unconfirmed

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	7.7

Partial Response

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	7.7

Stable Disease

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	0

Progression

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	3.8

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 Secondary · Up to 30 days after last intervention, up to 12.5 months or 1.04 years

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,

Allergic reaction

Group	Value	95% CI
Grade 3	3.8
Grade 4	0
Grade 5	0

Anemia

Group	Value	95% CI
Grade 3	69.2
Grade 4	3.8
Grade 5	0

Febrile neutropenia

Group	Value	95% CI
Grade 3	42.3
Grade 4	3.8
Grade 5	0

Leukopenia

Group	Value	95% CI
Grade 3	0
Grade 4	84.6
Grade 5	0

Lymphopenia

Group	Value	95% CI
Grade 3	38.5
Grade 4	0
Grade 5	0

Neutropenia

Group	Value	95% CI
Grade 3	0
Grade 4	88.5
Grade 5	0

Thrombocytopenia

Group	Value	95% CI
Grade 3	50
Grade 4	7.7
Grade 5	0

Thrombosis

Group	Value	95% CI
Grade 3	15.4
Grade 4	0
Grade 5	0

Overall Survival (OS) Secondary · Time from treatment start date until date of death or date last follow-up, up to 250 months

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.

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	89.7	32.4 – 245.8

Progression Free Survival (PFS) in Participants Who Received Idiotype Vaccine Secondary · Time from treatment start date until date of disease relapse or progression, death, or date last follow-up, an average of 25 months

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

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	25.0	8.8 – 245.8

Percentage of Participants With Antibodies to Keyhole Limpet Haemocyanin (KLH) Secondary · After vaccinations administered at 0, 1, 2, 3 and 5 months

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.

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	74

Percentage of Participants With Induction of Type 1 Cytokine T-cell Response Secondary · After vaccinations administered at 0, 1, 2, 3 and 5 months

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.

Peripheral blood mononuclear cells (PBMC)

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	87

Granulocyte macrophage colony-stimulating factor (GM-CSF)

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	65

Tumor necrosis factor α (TNFα)

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	52

Interferon-gamma (IFN-γ)

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	74

Time to Recovery of CD4 T Lymphocytes (CD4+) Secondary · After chemotherapy before vaccination, up to 6 months

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

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	3	2.8 – 5.4

Here is the Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0). Secondary · Up to 30 days after last intervention, up to 12.5 months or 1.04 years

Here is the number of participants with serious and/or non-serious adverse events 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 outc

Group	Value	95% CI
Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab	26

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 30 days after last intervention, up to 12.5 months or 1.04 years for serious and/or non-serious adverse events and up to 250 months for all-cause mortality.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, and Rituximab

Serious: 14/26 (54%)

Deaths: 17/26

Serious adverse events (4 terms)

Reaction	System	Etoposide, Prednisone, Vin…
Febrile neutropenia	Infections and infestations	—
Infection	Infections and infestations	—
Anemia	Blood and lymphatic system disorders	—
Infusion related reaction	General disorders	—

Other adverse events (81 terms — click to expand)

Reaction	System	Etoposide, Prednisone, Vin…
Constipation	Gastrointestinal disorders	—
Fatigue	General disorders	—
Sensory neuropathy	Nervous system disorders	—
Anemia	Blood and lymphatic system disorders	—
Stomatitis	Gastrointestinal disorders	—
Bone pain	Musculoskeletal and connective tissue disorders	—
Neutropenia	Blood and lymphatic system disorders	—
Leukopenia	Blood and lymphatic system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Diarrhea	Gastrointestinal disorders	—
Death unrelated to research and related to disease progression	General disorders	—
Taste disturbance	Gastrointestinal disorders	—
Anorexia	Gastrointestinal disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Nausea	Gastrointestinal disorders	—
Lymphopenia	Blood and lymphatic system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Febrile neutropenia	Infections and infestations	—
Hyperglycemia	Metabolism and nutrition disorders	—
Anxiety	Psychiatric disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Headache	Nervous system disorders	—
Muscle weakness	Musculoskeletal and connective tissue disorders	—
Alkaline phosphatase elevation	Hepatobiliary disorders	—
Depression	Nervous system disorders	—
Edema	Cardiac disorders	—
Vomiting	Gastrointestinal disorders	—
Abdominal pain	Gastrointestinal disorders	—
Infection	Infections and infestations	—
Rash	Skin and subcutaneous tissue disorders	—
Weight loss	General disorders	—
Fever	General disorders	—
Motor neuropathy	Nervous system disorders	—
SGOT elevation	Hepatobiliary disorders	—
SGPT elevation	Hepatobiliary disorders	—
Blurred vision	Eye disorders	—
Dizziness	Nervous system disorders	—
Hypoalbuminemia	Metabolism and nutrition disorders	—

Most-reported serious reactions: Febrile neutropenia, Infection, Anemia, Infusion related reaction.

Data from ClinicalTrials.gov NCT00005780 adverse events section.

Sponsor's own description

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....

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Doxorubicin pharmacokinetics and toxicity in patients with aggressive lymphoma and hepatic impairment.
   Lai C, Cole DE, Steinberg SM, Lucas N, et al · · 2023 · cited 10× · PMID 35882475 · DOI 10.1182/bloodadvances.2022007431