Clinical trial NCT00915408: A Dose Escalation Study of the Combination of Lenalidomide (Revlimid®), Dexamethasone and Cyclophosphamide in Patients Refractory or Relapsing From Stable Disease With Multiple Myeloma
Official title: A Phase I Dose Escalation Study of the Combination of Lenalidomide (Revlimid®), Dexamethasone and Cyclophosphamide in Patients Refractory or Relapsing From Stable Disease With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Cyclophosphamide
Dexamethasone
Lenalidomide
Lead sponsor: King's College Hospital NHS Trust
Sponsor class: OTHER
First posted: 2009-06-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose (MTD) and to evaluate the safety of cyclophosphamide when given on days 1 and 8 in a 28 day cycle in doses starting at 300mg ranging to 700mg in combination with Lenalidomide (Revlimid®) plus dexamethasone in patients who present with relapsed or refractory myeloma.


Eligibility criteria: Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age \>18 years at the time of signing the informed consent form.
3. Proven diagnosis of multiple myeloma.
4. Relapse or Refractory disease with evidence of progression after at least 2 cycles of anti-myeloma treatment.
5. Relapse or refractory disease with evidence of progressive disease after at least 1 previous therapy this may include consolidation of induction with a stem cell transplant).
6. Subjects may have been previously treated with thalidomide and/or radiation therapy. In addition, radiation therapy initiated prior to or at baseline (Day 1) must be complete prior to the initiation of therapy. The initiation of radiation therapy after baseline (Day 1) will be considered to be a treatment failure (except when given to treat or to promote the healing of a pathological fracture).
7. Measurable levels of myeloma paraprotein in serum (\>5 gms/L) or urine \> 2 g excreted in a 24-hour collection sample).
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
9. Able to adhere to the study visit schedule and other protocol requirements.
10. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10 - 14 days and again within 24 hours of starting study drug. In addition, sexually active WCBP must agree continued abstinence from heterosexual intercourse or to use adequate contraceptive methods starting 4 weeks prior to the initiation of therapy. WCBP must agree to have pregnancy tests weekly for the first 4 weeks, then monthly while on study drug (every 14 days for women with irregular cycles) and 4 weeks after the last dose of study drug. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy.
11. Disease free of prior malignancies for equal to or over 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast.
12. Able to receive low dose aspirin (e.g. 75mg) as prophylactic anticoagulant medication to prevent thromboembolism unless contraindicated. If low dose aspirin is contraindicated, subjects will receive another form of anticoagulant prophylaxis according to hospital guidelines.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or lactating females.
3. Any of the following laboratory abnormalities:

   1. Absolute neutrophil count (ANC) \<1.000 cells/mm3 (1.0 x 109/L)
   2. Platelet count \<.75.000/mm3 (75 x 109L)
   3. Serum creatinine \>2.5 mg/dL (221 umol/L)
   4. Serum SGOT/AST or SGPT/ALT \>3.0 x upper limit of normal (ULN)
   5. Serum total bilirubin \>2.0 mg/dL (34 umol/L)
4. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
5. Known hypersensitivity to thalidomide, dexamethasone or cyclophosphamide.
6. Prior history of uncontrollable side effects to dexamethasone therapy
7. The development of a desquamating rash while taking thalidomide
8. Any prior use of Lenalidomide (Revlimid®)
9. Use of any standard/experimental anti-myeloma drug therapy within 28 days of entry or use of any experimental non-drug therapy (e.g. donor leukocyte/mononuclear cell infusions) within 56 days of entry.

Primary outcomes:
measure: Dose limiting toxicity defined as: a) NCI Grade 4 haematological toxicity b) NCI Grade ¾ non-haematological toxicity
timeFrame: Weekly for first cycle
measure: Safety (type, frequency, severity, and relationship of adverse events)
timeFrame: Weekly for first cycle then monthly
Secondary outcomes:
measure: Time to progression
timeFrame: Monthly
measure: Paraprotein response
timeFrame: Monthly
measure: Bone marrow response
timeFrame: Baseline, end of treatment and disease progression
measure: Duration of response
timeFrame: Monthly
measure: Overall survival
timeFrame: Monthly
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: King's College Hospital NHS Trust
name: Steve Schey, FRCP FRACP FRCPath
role: PRINCIPAL_INVESTIGATOR
References: