NCT00069238

Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas

Completed Phase 2 Results posted Last updated 24 February 2022

What this trial tests

Phase 2 trial testing Alemtuzumab (Campath) in Lymphoma, T-Cell in 31 participants. Completed in 17 March 2021.

Timeline

19 September 2003

Primary endpoint
11 June 2009

17 March 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	31
Start date	19 September 2003
Primary completion	11 June 2009
Estimated completion	17 March 2021
Sites	1 location across United States

Drugs / interventions tested

• Alemtuzumab (Campath) — full drug profile →
• EPOCH — full drug profile →

Conditions studied

• Lymphoma, T-Cell — all drugs for Lymphoma, T-Cell →
• Lymphoma, Extranodal NK-T-Cell — all drugs for Lymphoma, Extranodal NK-T-Cell →

Sponsor

National Cancer Institute (NCI)

Who can join

17 and older, any sex, with Lymphoma, T-Cell or Lymphoma, Extranodal NK-T-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.

Maximum Tolerated Dose (MTD) of Alemtuzumab Primary · up to 2 cycles of therapy, approximately 42 days

MTD was achieved by increasing doses of Alemtuzumab on three cohorts. Cohort 1 received 30mg of Alemtuzumab, cohort 2 received 60mg of Alemtuzumab, and cohort 3 received 90mg of Alemtuzumab intravenously up to 2 cycles. The MTD reflects the highest dose of Alemtuzumab in which no more than 1 of 6 participants entered at a specific dose level experienced a dose limiting toxicity (DLT).

Group	Value	95% CI
All Participants	30

Number of Participants With Adverse Events Primary · 67 months and 9 days

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Group	Value	95% CI
All Participants	31

Clinical Response Secondary · From date of onstudy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 67 months and 9 days.

Response was measured by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (Cru)is as per complete remission criterion except that if a residual node is greater than 1.5cm, it must have decreased by greater than 75% in the sum of the products of the perpendicular diameters (SPD). Partial response (PR) is ≥50% decrease in the SPD of 6 largest dominant nodes or nodal masses. Progressive disease (PD) is ≥50% increas

Group	Value	95% CI
All Participants	17
All Participants	0
All Participants	7
All Participants	2

Adverse events — posted to ClinicalTrials.gov

Time frame: 67 months and 9 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

All Participants

Serious: 23/31 (74%)

Deaths: 23/31

Serious adverse events (10 terms)

Reaction	System	All Participants
DEATH:: Death due to progression	General disorders	—
DEATH:: Death related to the study	General disorders	—
HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Upper GI Not otherwise specified (NOS)	Blood and lymphatic system disorders	—
INFECTION:: Febrile neutropenia	Infections and infestations	—
INFECTION:: Infection	Infections and infestations	—
INFECTION:: Infection (documented clinically or microbiologically)	Infections and infestations	—
INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils	Infections and infestations	—
INFECTION:: Infection with unknown ANC:: Blood	Infections and infestations	—
RENAL/GENITOURINARY:: Cystitis	Renal and urinary disorders	—
RENAL/GENITOURINARY:: Urinary frequency/urgency	Renal and urinary disorders	—

Other adverse events (173 terms — click to expand)

Reaction	System	All Participants
BLOOD/BONE MARROW:: Leukocytes (total white blood count (WBC))	Blood and lymphatic system disorders	—
BLOOD/BONE MARROW:: Lymphopenia	Blood and lymphatic system disorders	—
BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC)	Blood and lymphatic system disorders	—
BLOOD/BONE MARROW:: Hemoglobin	Blood and lymphatic system disorders	—
BLOOD/BONE MARROW:: Platelets	Cardiac disorders	—
NEUROLOGY:: Neuropathy: sensory	Nervous system disorders	—
GASTROINTESTINAL:: Mucositis/stomatitis (clinical exam):: Oral cavity	Gastrointestinal disorders	—
METABOLIC/LABORATORY:: Albumin, serum-low (hypoalbuminemia)	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Calcium, serum-low (hypocalcemia)	Metabolism and nutrition disorders	—
CONSTITUTIONAL SYMPTOMS:: Fatigue (asthenia, lethargy, malaise)	General disorders	—
GASTROINTESTINAL:: Nausea	Gastrointestinal disorders	—
METABOLIC/LABORATORY:: Magnesium, serum-low (hypomagnesemia)	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Glucose, serum-high (hyperglycemia)	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Potassium, serum-low (hypokalemia)	Metabolism and nutrition disorders	—
INFECTION:: Febrile neutropenia	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Alkaline phosphatase	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Phosphate, serum-low (hypophosphatemia)	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: Sodium, serum-low (hyponatremia)	Metabolism and nutrition disorders	—
DERMATOLOGY/SKIN:: Hair loss/alopecia (scalp or body)	Skin and subcutaneous tissue disorders	—
METABOLIC/LABORATORY:: Magnesium, serum-high (hypermagnesemia)	Metabolism and nutrition disorders	—
GASTROINTESTINAL:: Diarrhea	Gastrointestinal disorders	—
METABOLIC/LABORATORY:: ALT, SGPT (serum glutamic pyruvic transaminase)	Metabolism and nutrition disorders	—
METABOLIC/LABORATORY:: AST, SGOT(serum glutamic oxaloacetic transaminase)	Metabolism and nutrition disorders	—
GASTROINTESTINAL:: Vomiting	Gastrointestinal disorders	—
PAIN:: Pain:: Head/headache	Nervous system disorders	—
GASTROINTESTINAL:: Constipation	Gastrointestinal disorders	—
PAIN:: Pain:: Bone	Musculoskeletal and connective tissue disorders	—
CONSTITUTIONAL SYMPTOMS	General disorders	—
GASTROINTESTINAL:: Anorexia	Gastrointestinal disorders	—
METABOLIC/LABORATORY:: Bilirubin (hyperbilirubinemia)	Metabolism and nutrition disorders	—
PAIN:: Pain:: Muscle	Musculoskeletal and connective tissue disorders	—
ALLERGY/IMMUNOLOGY:: Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	Immune system disorders	—
CARDIAC GENERAL:: Hypotension	Cardiac disorders	—
CONSTITUTIONAL SYMPTOMS:: Rigors/chills	General disorders	—
DERMATOLOGY/SKIN:: Rash/desquamation	Skin and subcutaneous tissue disorders	—
METABOLIC/LABORATORY:: Potassium, serum-high (hyperkalemia)	Metabolism and nutrition disorders	—
NEUROLOGY:: Dizziness	Nervous system disorders	—
ALLERGY/IMMUNOLOGY:: Allergic reaction/hypersensitivity (including drug fever)	Immune system disorders	—
CONSTITUTIONAL SYMPTOMS:: Weight loss	General disorders	—
GASTROINTESTINAL:: Mucositis/stomatitis (functional/symptomatic):: Oral cavity	Gastrointestinal disorders	—

Most-reported serious reactions: DEATH:: Death due to progression, DEATH:: Death related to the study, HEMORRHAGE/BLEEDING:: Hemorrhage, GI:: Upper GI Not otherwise specified (NOS), INFECTION:: Febrile neutropenia, INFECTION:: Infection, INFECTION:: Infection (documented clinically or microbiologically), INFECTION:: Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils, INFECTION:: Infection with unknown ANC:: Blood.

Data from ClinicalTrials.gov NCT00069238 adverse events section.

Sponsor's own description

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkins lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkin s lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objectives:

Determine the toxicity of Alemtuzumab and etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy in untreated cluster of differentiation 52 (CD52)-expressing T and natural killer (NK) lymphoid malignancies.

Determine the maximum tolerated dose of Alemtuzumab administered in combination with EPOCH chemotherapy.

Determine in a preliminary fashion the anti-tumor activity of the combination of Alemtuzumab and EPOCH chemotherapy.

Eligibility:

CD52-expressing lymphoid malignancy.

Patients with chemotherapy naive aggressive T \& NK lymphomas. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Adequate organ function, unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart. failure within the past year.

Human immunodeficiency virus (HIV) negative.

Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in a preliminary fashion the antitumor activity of the combination with Dose-Adjusted EPOCH.

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each. Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed by dose-adjusted EPOCH chemotherapy days 1-5.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.
   Škubník J, Pavlíčková VS, Ruml T, Rimpelová S. · · 2021 · cited 86× · PMID 34571726 · DOI 10.3390/biology10090849
2. Tissue-Resident and Recruited Macrophages in Primary Tumor and Metastatic Microenvironments: Potential Targets in Cancer Therapy.
   Cotechini T, Atallah A, Grossman A. · · 2021 · cited 49× · PMID 33924237 · DOI 10.3390/cells10040960
3. Novel targeted therapies of T cell lymphomas.
   Iżykowska K, Rassek K, Korsak D, Przybylski GK, et al · · 2020 · cited 49× · PMID 33384022 · DOI 10.1186/s13045-020-01006-w
4. T-cell lymphomas, a challenging disease: types, treatments, and future.
   Ma H, Abdul-Hay M. · · 2017 · cited 30× · PMID 27743148 · DOI 10.1007/s10147-016-1045-2
5. Novel target and treatment agents for natural killer/T-cell lymphoma.
   Tian XP, Cao Y, Cai J, Zhang YC, et al · · 2023 · cited 19× · PMID 37480137 · DOI 10.1186/s13045-023-01483-9
6. Updating targets for natural killer/T-cell lymphoma immunotherapy.
   Xue W, Zhang M. · · 2021 · cited 19× · PMID 33628584 · DOI 10.20892/j.issn.2095-3941.2020.0400
7. Advances and challenges of immunotherapies in NK/T cell lymphomas.
   He L, Chen N, Dai L, Peng X. · · 2023 · cited 12× · PMID 38026157 · DOI 10.1016/j.isci.2023.108192
8. 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