A Study of Low Dose Lenalidomide and Dexamethasone in Relapsed/Refractory Myeloma in Patients at High Risk for Myelosuppression

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Peter MacCallum Cancer Centre, Australia
ClinicalTrials.gov Identifier:
NCT00482261
First received: June 3, 2007
Last updated: January 8, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to see whether combination of low dose lenalidomide(10mg)+ dexamethasone is equally effective in treating relapsed/refractory myeloma in the group of elderly patients and other patients at risk of myelosuppression, whilst producing less side effects, especially myelosuppression compared to the higher dose of lenalidomide of 25mg used in the MM-009 and MM-010 trials.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: dexamethasone
Drug: aspirin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Low Dose Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma (Rev-Lite) in Patients at High Risk for Myelosuppression

Resource links provided by NLM:


Further study details as provided by Peter MacCallum Cancer Centre, Australia:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time To Progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Safety and toxicity [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • Prognostic factors associated with ORR, TTP, OS [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Compare OTT, TTP an toxicities to MM-009/MM-010 data [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 150
Study Start Date: June 2007
Estimated Study Completion Date: September 2013
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: len-dex
Drug: Lenalidomide 15mg daily, days 1-21 of a 28 day cycle for 4 cycles. Patients who get stable disease or better will then receive 15mg on days 1-21 from cycle 5 onwards; Drug: dexamethasone 20mg day 1-4, 9-12, 17-20 for 4 cycles. Patients who get stable disease or better will then get dexamethasone 20mg on days 1-4 of a 28 day cycle, from cycle 5 onwards
Drug: Lenalidomide
15mg daily, days 1-21 of a 28 day cycle for 4 cycles. Patients who get stable disease or better will then receive 15mg on days 1-21 from cycle 5 onwards
Drug: dexamethasone
20mg day 1-4, 9-12, 17-20 for 4 cycles. Patients who get stable disease or better will then get dexamethasone 20mg on days 1-4 of a 28 day cycle, from cycle 5 onwards
Drug: aspirin
100mg/day

Detailed Description:

Lenalidomide has proven efficacy in myeloma. In the Phase I studies with lenalidomide monotherapy, responses were observed at doses of 5mg, 10mg and 25mg. The dose limiting toxicity of lenalidomide monotherapy was myelosuppression·

In the International MM-010 and MM-009 studies, lenalidomide was administered at 25mg d1-d21 (with pulse dexamethasone) of a 28 day cycle. Although the overall response rate and time to progression were impressive, a significant toxicity was myelosuppression. The average age in these 2 studies was approximately 63 years, some 7 years lower than the median age for myeloma. The median number of prior therapies was 2. Thus, if lenalidomide therapy is to be optimally applied in an older and/or more heavily pre-treated population, a simpler, less toxic regimen would be valuable. Low dose (15mg) lenalidomide (Rev-Lite) with dexamethasone may achieve this goal·

Based on analysis of the MM009 and MM010 data the patients at highest risk for myelosuppression and subsequent dose reduction were those over the age of 60 years (approx 30% risk which increased to approx 50% by 70 years).It is hypothesized that patients with lower base-line platelets may also be at higher risk of lenalidomide-induced myelosuppression. Little is known about lenalidomide tolerance in patients with impaired renal function, consequently patients with relatively poorer renal function will also be enrolled into this study.

  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 consent form.
  2. Must meet one of following age group requirements at the time of signing consent form.

    1. age 18-59 years
    2. >59 years
  3. Patients 18-59 years are eligible only if:

    • platelets between 50-74x109/L or
    • calculated GFR between 20ml/min and 59ml/min
  4. Able to adhere to the study visit schedule and other protocol requirements.
  5. Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria.
  6. Must have relapsed or refractory disease.
  7. Measurable disease, defined as follows:

    • For secretory multiple myeloma: measurable disease is defined as any quantifiable serum monoclonal protein value (generally, but not necessarily, >5g/L of M-Protein). If the M band is <5g/L, then the serum free light chains(SFLC) must be assessed and if >100mg/L will also be used to measure disease response. Where applicable, urine light-chain excretion of ≥200 mg/24 hours will also be used to measure disease response.
    • For light chain disease (M band in serum <5g/L but measurable FLC in urine): measurable disease is defined by either urine FLC OR the presence of serum FLC (must be >100mg/L). Investigators can use either test (or both) but must use the same method throughout the trial.
    • For non-secretory multiple myeloma (no M-protein in serum or urine by immunofixation): measurable disease is defined by soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan).
  8. Patient has a life-expectancy ≥3 months.
  9. All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
  10. ECOG performance status of ≤2 at study entry
  11. Laboratory test results within these ranges:

    • Absolute neutrophil count ³ 1.0 x 109/L (can be supported with growth factor)
    • Total bilirubin ≤1.5 mg/dL
    • AST (SGOT) or ALT (SGPT) ≤2 x UL
  12. For females subjects:

    • Must have two negative pregnancy tests (sensitivity ≥ 50 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug.
    • Females of childbearing potential (FCBP)† must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
  13. Male Subjects:

    • Must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.
    • Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure.
  14. Disease free of prior malignancies for ≥3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast.
  15. Able to take aspirin daily as prophylactic anticoagulation. (patients intolerant to ASA may use low molecular weight heparin).

Exclusion Criteria:

  1. Dexamethasone resistant myeloma based on last therapy. Patients are defined as being refractory to high-dose dexamethasone if they achieved less than a partial response, or developed progressive disease within 6 months of discontinuing dexamethasone, or dexamethasone was discontinued because of ≥Grade 3 dexamethasone-related toxicity. High-dose dexamethasone therapy is defined as >500mg dexamethasone or equivalent over a 10-week period, whether administered alone or as part of the VAD regimen.
  2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  3. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  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. Use of any other experimental drug or therapy within 28 days of baseline.
  6. Known hypersensitivity to thalidomide.
  7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  8. Any prior use of lenalidomide.
  9. Concurrent use of other anti-cancer agents or treatments.
  10. Known positive for HIV or infectious hepatitis, type A, B or C.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00482261

Locations
Australia, Victoria
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3002
Sponsors and Collaborators
Peter MacCallum Cancer Centre, Australia
Celgene Corporation
Investigators
Principal Investigator: Miles H Prince, MD Peter MacCallum Cancer Centre, Australia
  More Information

No publications provided

Responsible Party: Peter MacCallum Cancer Centre, Australia
ClinicalTrials.gov Identifier: NCT00482261     History of Changes
Other Study ID Numbers: RV-PI-0103, 07/04
Study First Received: June 3, 2007
Last Updated: January 8, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Peter MacCallum Cancer Centre, Australia:
myeloma
relapse
refractory
elderly
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
Aspirin
Dexamethasone acetate
Dexamethasone
BB 1101
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 15, 2014