Phase II Study of Lenalidomide for the Treatment of Relapsed or Refractory Hodgkin's Lymphoma
18 Years
N/A
Both
Hodgkin Disease
Trial Information
Phase II Study of Lenalidomide for the Treatment of Relapsed or Refractory Hodgkin's Lymphoma
While the results of primary therapy for Hodgkin's lymphoma are generally excellent, between
10-20% of patients with advanced stage disease will not enter a complete remission (CR) and
between 20-30% of patients will relapse after completion of treatment. Salvage chemotherapy
followed by high dose chemotherapy and autologous stem cell transplantation (ASCT) has
become the treatment of choice in patients with relapsed or initially
chemotherapy-refractory disease.
Although high dose chemotherapy remains a curative option for the treatment of relapsed or
chemotherapy-refractory Hodgkin's lymphoma, up to 50% of patients will ultimately recur
post-stem cell transplant and will require further treatment.
Thalidomide is an agent that has anti-inflammatory, immunomodulatory and anti-angiogenic
properties. Thalidomide has been shown to have activity in a number of solid and hematologic
malignancies, and has demonstrated effectiveness in the treatment of refractory multiple
myeloma. A dose escalation study of single-agent thalidomide has been performed in heavily
pre-treated patients in which two Hodgkin's patients were enrolled and did not respond to
treatment. Based on the NCI experience with vinblastine, we initiated a phase II trial
examining the combination of thalidomide and vinblastine in patients who were being treated
palliatively for Hodgkin's lymphoma. In a heavily pre-treated group of patients (70% of
cases having relapsed post-ASCT), a response rate of 40% to the combination was noted with
median duration of response of over nine months.
Lenalidomide (Revlimid®) is a thalidomide derivative and the first-in-class novel
immunomodulatory agent that has more potent activity as well as a more favourable toxicity
profile than the parent compound. Based on the alterations demonstrated in various cytokines
and angiogenic markers in patients with Hodgkin's lymphoma, we feel that Lenalidomide's
immunomodulatory and anti-angiogenic effects make this an ideal drug to study in this
lymphoma. This will be the first study to assess Lenalidomide in patients with Hodgkin's
lymphoma.This is a single arm, open-label phase II multi-centre study evaluating the single
agent activity of Lenalidomide in relapsed or refractory Hodgkin's lymphoma. The primary
endpoint is objective response rate (CR + CRu + PR) as determined by International Workshop
Criteria.
Initial treatment will consist of lenalidomide 25 mg PO daily given for 21 consecutive days
(days 1 - 21), with seven days off on a 28 day cycle.Patients with PR, CR or CRu, may
continue on therapy for 2 cycles past best response.Patients with PD at any time or those
with evidence of SD after cycle 4 of monotherapy will be eligible to receive treatment with
dexamethasone 40 mg PO daily on days 1 - 4 and 15 - 18 of a 28 day cycle while continuing
protocol treatment if they continue to meet the criteria of continuation on therapy.
Inclusion Criteria:
- Histologically confirmed Hodgkin's lymphoma that is relapsed or refractory (repeat
biopsy is not mandatory) and is no longer eligible for curative treatment
-
- Patients with disease progression after ASCT will be eligible if they have received
- ECOG Performance Status 0-2
- Adequate hematological function:
- Absolute granulocyte count > 1.0 x 10 to the 9/L
- Platelet count > 75 x 10 to the 9/L
- Adequate renal and hepatic functions:
- Serum creatinine < 1.25 x UNL or a calculated creatinine clearance > 50 mL/min
- Serum bilirubin < 1.5 x UNL and AST/ALT < 3 x UNL
- Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and
repeated within 24 hours of starting study drug 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 4 weeks before she starts taking lenalidomide. Women must also agree
to ongoing pregnancy testing. Men must agree not to father a child and agree to use a
condom if his partner is of child bearing potential. (See Appendix B Pregnancy
Testing Guidelines and Acceptable Birth Control Methods.)
- Able to take aspirin (325 mg daily) as prophylactic anticoagulation (patients
intolerant to ASA may use warfarin or low molecular weight heparin)
- Written Informed Consent must be given according to ICH/GCP and national/local
regulations
Exclusion Criteria
- Prior treatment with Lenalidomide or Thalidomide
- Use of any other experimental therapy within the 28 days prior to baseline assessment
- Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C
- Pregnant or Lactating women
- Other significant medical problems such as uncontrolled hypertension, uncontrolled
psychiatric symptoms disorders, serious infections, active peptic ulcer disease, or
any other medical conditions that might be aggravated by treatment
- Second malignancy in the past five years with the exception of adequately treated
basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the
trial
- Before patient registration, written informed consent must be given according to
ICH/GCP, and national/local regulations.
- Concurrent use of other anti-cancer agents or treatments.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To assess the response rate (CR + CRu + PR) of Lenalidomide given as a daily oral dose of 25 mg on days 1 - 21 followed by 7 days of no therapy of a 28 day cycle in the treatment of a population with relapsed or refractory Hodgkin's lymphoma
Outcome Time Frame:
CT scans performed every two months while on therapy
Safety Issue:
No
Principal Investigator
John Kuruvilla
Investigator Role:
Principal Investigator
Investigator Affiliation:
Princess Margaret Hospital, Canada
Authority:
Canada: Ethics Review Committee
Study ID:
CC-5013-HL
NCT ID:
NCT00478959
Start Date:
December 2006
Completion Date:
December 2012
Related Keywords:
- Hodgkin Disease
- Lenalidomide
- Revlimid
- Hodgkin's
- Hodgkin
- Hodgkin's Lymphoma
- Hodgkin's Disease
- Lymphoma
- Hodgkin Disease
- Lymphoma
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