Study of RAD001 in Patients With Relapsed/Refractory Hodgkin Lymphoma That Has Progressed After High-dose Chemotherapy and Autologous Stem Cell Transplant and/or After Gemcitabine- or Vinorelbine- or Vinblastine-based Treatment.

An Open-label, Single-arm Phase II Study of RAD001 in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01022996

Enrollment

Registered

2009-12-01

Start date

2009-12-31

Completion date

2014-11-30

Last updated

2016-05-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hodgkin Lymphoma

Keywords

Hodgkin's Lymphoma, Hodgkin Lymphoma, Hodgkin's Disease, Hodgkin Disease, Lymphoma, Lymphoproliferative Disorders, Neoplasms by Histological type, Lymphatic Diseases, Hemic and Lymphatic Diseases, Recurrent Lymphoma, Refractory Lymphoma, Relapsed Lymphoma, Classical Hodgkin Lymphoma, Classical Hodgkin's Disease, Nodular sclerosing Hodgkin Lymphoma, Mixed-cellularity Hodgkin Lymphoma, Lymphocyte-rich Hodgkin Lymphoma, Lymphocyte depleted Hodgkin Lymphoma

Brief summary

This study will assess RAD001 in patients with refractory or relapsed Hodgkin Lymphoma that has progressed after high-dose chemotherapy and Autologous Stem cell transplant and/or after gemcitabine- or vinorelbine- or vinblastine-based treatment.

Interventions

DRUGEverolimus (RAD001)

Everolimus (RAD001) 10 mg (two 5mg tablets) given orally once daily and packed in blisters.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patients with a history of classical Hodgkin's lymphoma that has progressed after high-dose chemotherapy and Autologous Stem cell transplant and/or after gemcitabine- or vinorelbine- or vinblastine-based treatment * Patients with at least one site of measurable disease measuring ≥ 2.0cm confirmed by PET and CT Scan (or MRI) * Patients with adequate bone marrow, liver and renal function (confirmed by laboratory values) * Patients with fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN

Exclusion criteria

* Previous treatment with mTOR inhibitors * Prior allogeneic stem cell transplant * Chemotherapy, monoclonal antibody therapy, major surgery or treatment with other investigational drugs within 4 weeks of starting study treatment * Another malignancy within 3 years of study entry (except adequately treated non-melanoma skin cancer and carcinoma in situ of the cervix) * Severe and/or uncontrolled medical conditions that could affect participation in this study * Female patients who are pregnant or breastfeeding; patients who are not willing to use adequate birth control during the study and for 8 weeks after the last study treatment Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Overall Response Rate (ORR) Based on the Assessments by Investigator	at screening and every threee months beginning at cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	ORR: % of patients whose overall disease response was a complete response (CR) or a partial response (PR) in 8 cycles CR: Complete normalization of all index nodal & extranodal lesions: Radiological regression to normal size of all lymph nodes & nodal masses & complete disappearance of all lesions PR: At least a 50% decrease in the SPD of all index nodal & extranodal lesions FDG-avid or PET positive prior to therapy: one or more PET positive at previously involved site.At least a 50% increase in the SPD of all index nodal & extranodal lesions, taking as reference the smallest sum of the product of the diameters of all index lesions recorded at or after baseline . Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Unknown (UNK): Progression not documented & one or more of the index lesions not assessed or assessed using a different method than baseline at the time of radiologic evaluation. Each cycle was 28 days.

Secondary

Measure	Time frame	Description
Time to Overall Response (TTR) Per Kaplan-Meier Estimate	Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	Time to overall response was defined as the time from the first date of treatment to the date of first documented response of CR or PR. Time to overall response is applied to patients whose best overall response is CR or PR. Patients who drop-out or did not have a response (CR or PR) will be treated as censored at the date of last adequate tumor assessment.
Duration of Overall Response (DoR)	Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	The duration of overall response was calculated from the date of first documented response (CR or PR) to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy. This only applies to patients whose best overall response is CR or PR.
Disease Control Rate (DCR)	Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	The disease control rate was defined as the percentage of patients with a best overall response of CR, PR or stable disease (SD).
Duration of Disease Control	Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	The duration of overall response (CR/PR) was applied only to patients whose best overall response was CR or PR. Duration of overall response was calculated from the date of the first documented response of CR or PR to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy.
Progression Free Survival (PFS) by Kaplan-Meier Estimate	Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason	Progression-free survival (PFS) was defined as the time from the first date of treatment to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy. An event for PFS was defined as a documented disease progression or death due to any cause or start of a new antineoplastic therapy, whichever occurred first. Cycle = 28 days.

Countries

United States

Participant flow

Participants by arm

Arm	Count
RAD001 Patients with a history of classical Hodgkin lymphoma (ie, nodular sclerosing, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) whose disease had progressed after receiving high-dose chemotherapy with AHSCT (if eligible) and/or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen, were enrolled into this study. Patients had at least one site of measurable disease at baseline ≥ 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan. Patients received 10 mg of everolimus (two 5 mg tablets), self-administered orally once daily (qd), continuously from Cycle 1 Day 1 until progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason. The treatment cycle consisted of 28 days.	57
Total	57

Arm

Count

RAD001

Patients with a history of classical Hodgkin lymphoma (ie, nodular sclerosing, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) whose disease had progressed after receiving high-dose chemotherapy with AHSCT (if eligible) and/or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen, were enrolled into this study. Patients had at least one site of measurable disease at baseline ≥ 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan. Patients received 10 mg of everolimus (two 5 mg tablets), self-administered orally once daily (qd), continuously from Cycle 1 Day 1 until progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason. The treatment cycle consisted of 28 days.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative problems	6
Overall Study	Adverse Event	14
Overall Study	Disease Progression	32
Overall Study	Lost to Follow-up	1
Overall Study	Protocol Violation	1
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	RAD001
Age, Continuous	36.33 years STANDARD_DEVIATION 14.101
Sex: Female, Male Female	33 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	56 / 57
serious Total, serious adverse events	18 / 57

Outcome results

Primary

Overall Response Rate (ORR) Based on the Assessments by Investigator

ORR: % of patients whose overall disease response was a complete response (CR) or a partial response (PR) in 8 cycles CR: Complete normalization of all index nodal & extranodal lesions: Radiological regression to normal size of all lymph nodes & nodal masses & complete disappearance of all lesions PR: At least a 50% decrease in the SPD of all index nodal & extranodal lesions FDG-avid or PET positive prior to therapy: one or more PET positive at previously involved site.At least a 50% increase in the SPD of all index nodal & extranodal lesions, taking as reference the smallest sum of the product of the diameters of all index lesions recorded at or after baseline . Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Unknown (UNK): Progression not documented & one or more of the index lesions not assessed or assessed using a different method than baseline at the time of radiologic evaluation. Each cycle was 28 days.

Time frame: at screening and every threee months beginning at cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason

Population: Full analysis set (FAS) consisted of all patients who received at least 1 dose of study drug and was the primary set for efficacy analyses.

Arm	Measure	Group	Value (NUMBER)
RAD001	Overall Response Rate (ORR) Based on the Assessments by Investigator	Complete response (CR)	8.8 percentage of participants
RAD001	Overall Response Rate (ORR) Based on the Assessments by Investigator	Partial response (PR)	36.8 percentage of participants
RAD001	Overall Response Rate (ORR) Based on the Assessments by Investigator	Response of CR or PR	45.6 percentage of participants

Secondary

Disease Control Rate (DCR)

The disease control rate was defined as the percentage of patients with a best overall response of CR, PR or stable disease (SD).