A Dose Escalation Study of the Combination of Lenalidomide (Revlimid®), Dexamethasone and Cyclophosphamide in Patients Refractory or Relapsing From Stable Disease With Multiple Myeloma (CRD)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by King's College Hospital NHS Trust.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
King's College Hospital NHS Trust
ClinicalTrials.gov Identifier:
NCT00915408
First received: June 5, 2009
Last updated: NA
Last verified: June 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by King's College Hospital NHS Trust:

Primary Outcome Measures:
  • Dose limiting toxicity defined as: a) NCI Grade 4 haematological toxicity b) NCI Grade ¾ non-haematological toxicity [ Time Frame: Weekly for first cycle ] [ Designated as safety issue: Yes ]
  • Safety (type, frequency, severity, and relationship of adverse events) [ Time Frame: Weekly for first cycle then monthly ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to progression [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
  • Paraprotein response [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
  • Bone marrow response [ Time Frame: Baseline, end of treatment and disease progression ] [ Designated as safety issue: Yes ]
  • Duration of response [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: September 2006
Estimated Study Completion Date: April 2010
Estimated Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CRD Drug: Lenalidomide
Oral lenalidomide 25mg daily on Days 1-21 every 28 days cycles for up to 9 cycles. From Cycle 10 Lenalidomide 25mg orally on days 1-21, every 28 days.
Other Name: Revlimid
Drug: Dexamethasone
Dexamethasone 20mgs orally, daily on Days 1-4 and 8-11 repeated every 28 day cycles for up to 9 cycles.
Drug: Cyclophosphamide
Oral Cyclophosphamide will be added to the regime starting on days 1 and 8. The dose of Cyclophosphamide will be escalated in cohorts rising in 100mg increments from 300 to 700mgs days 1,and 8 every 28 day cycles for up to 9 cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00915408

Locations
United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom, SE5 9RS
Royal Marsden NHS Foundation Trust
London, United Kingdom, SM2 5PT
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Principal Investigator: Steve Schey, FRCP FRACP FRCPath King's College Hospital NHS Trust
  More Information

No publications provided

Responsible Party: Dr Steve Schey, King's College Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00915408     History of Changes
Other Study ID Numbers: 05CC15, REC - 06/Q1606/75, EudraCT - 2005-005145-19
Study First Received: June 5, 2009
Last Updated: June 5, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by King's College Hospital NHS Trust:
Multiple Myeloma
Cyclophosphamide
Dexamethasone
Lenalidomide

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014