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CompletedNCT00966693Updated Nov 4, 2020Results posted

Lenalidomide, Thalidomide and Dexamethasone in Treating Participants With Relapsed or Refractory Multiple Myeloma

A Phase 1/2 interventional study of Dexamethasone and Lenalidomide in Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, sponsored by M.D. Anderson Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-11-04.

Sponsored by M.D. Anderson Cancer Center · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
77
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase I/II trial studies the best dose and side effects of lenalidomide and thalidomide, and how well they work with dexamethasone in treating participants with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as lenalidomide, thalidomide and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of the combination of lenalidomide and thalidomide and dexamethasone (LTD) in patients with relapsed/refractory multiple myeloma (RRMM). (Phase 1) II. To determine the overall (complete remission [CR)]+ very good partial response [VGPR]+ partial response [PR)] response rate of the combination after 4 cycles of therapy. (Phase 2)

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR). (Phase 1) II. To determine the time to progression (TTP). (Phase 1) III. To determine the progression free survival (PFS). (Phase 1) IV. To determine the time to best response. (Phase 1) V. To determine the CR, VGPR. (Phase 2) VI. To determine the time to progression (TTP). (Phase 2) VII. To determine the progression free survival (PFS). (Phase 2) VIII. To determine the time to best response. (Phase 2) IX. To assess the safety of the combination of LTD in patients with RRMM. (Phase 2) X. Time to next therapy. (Phase 2) XI. Symptom measurement - multiple-symptom assessment tool. (Phase 2)

OUTLINE: This is a dose-escalation study of lenalidomide and thalidomide.

Participants receive lenalidomide orally (PO) on days 1-21 and thalidomide PO once daily (QD) on days 1-28. Participants also receive dexamethasone PO QD on days 1-4, 9-12, and 17-20 of courses 1-2, and days 1, 8, 15, and 22 of subsequent courses. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Participants who have stable or responding disease to treatment receive lenalidomide PO on days 1-21 and thalidomide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants may receive dexamethasone at the discretion of the investigator.

After completion of study treatment, patients are followed up at 30 days.

02

Conditions studied

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 77 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.

Of its 599 completed or terminated interventional studies of FDA-regulated products, 402 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Understand and voluntarily sign an informed consent form
  • Relapsed/refractory multiple myeloma (MM) with measurable levels of myeloma paraprotein in serum (>= 0.5 g/dl), urine (>= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio
  • Serum creatinine =\< 2.5 mg/dl

  • Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide 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 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

    • A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
  • Absolute neutrophil count > 1000 cells/mm\^3
  • Platelet count > 50,000 cells/mm\^3 for patients with \< 50% of bone marrow plasma cells and platelet count > 25,000 cells/mm\^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells
  • Total bilirubin =\< 2.0 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) \< 3 x upper limit of normal (ULN)
  • Able to take prophylactic anticoagulation, warfarin or equivalent agent
  • Patient is able to understand and comply with the terms and conditions of the lenalidomide and thalidomide counseling program
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist, AND the S.T.E.P.S. program

Exclusion criteria

Exclusion Criteria:

  • Any serious medical condition, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
  • Use of any cancer therapy within 21 days prior to beginning cycle 1 day 1 of therapy (radiation therapy allowed within 5 days of completion of radiation therapy).
  • Known hypersensitivity to thalidomide, lenalidomide and dexamethasone.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
77 participants (actual)

Study arms

  • Experimental
    Treatment (lenalidomide, thalidomide, dexamethasone)

    Participants receive lenalidomide PO on days 1-21 and thalidomide PO QD on days 1-28. Participants also receive dexamethasone PO QD on days 1-4, 9-12, and 17-20 of courses 1-2, and days 1, 8, 15, and 22 of subsequent courses. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Participants who have stable or responding disease to treatment receive lenalidomide PO on days 1-21 and thalidomide PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants may receive dexamethasone at the discretion of the investigator.

    Drug: Dexamethasone · Drug: Lenalidomide · Drug: Thalidomide

Interventions

  • DrugDexamethasone

    Given PO

    Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

  • DrugLenalidomide

    Given PO

    Also known as: CC-5013, CC5013, CDC 501, Revlimid

  • DrugThalidomide

    Given PO

    Also known as: (+)-Thalidomide, (-)-Thalidomide, .alpha.-Phthalimidoglutarimide, 2, 6-Dioxo-3-phthalimidopiperidine, Alpha-Phthalimidoglutarimide, Contergan, Distaval, Kevadon, N-(2,6-Dioxo-3-piperidyl)phthalimide, N-Phthaloylglutamimide, N-Phthalylglutamic Acid Imide, Neurosedyn, Pantosediv, Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)-, Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)-, Sedalis, Sedoval K-17, Softenon, Synovir, Talimol, Thalomid

06

What researchers measure

Primary outcomes

  1. Number of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

    To determine the dose limitations toxicities of the combination of lenalidomide and thalidomide and dexamethasone (LTD) in patients with relapsed/refractory multiple myeloma (RRMM).

    Time frame: After one 28-day cycle

  2. Complete Response(CR) and Very Good Partial Response(VGPR)

    To determine the best overall response (CR+VGPR+PR) of the lenalidomide, thalidomide, dexamethasone combination based on IMWG criteria at nadir.

    Time frame: Evaluated each 28-day cycle and nadir of criteria is considered best overall response (median time to best response for this study was 2 cycles (range for best overall response was 1-21 cycles).

Secondary outcomes

  1. Time to Progression

    Time to Progression was estimated using Kaplan Meier analysis.

    Time frame: Up to 9 years

  2. Progression Free Survival

    Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

    Time frame: Up to 9 years

  3. Time to Best Response

    Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

    Time frame: Up to 9 years

  4. Incidence of Adverse Events

    Linear regression was utilized to assess the effect of patient prognostic factors on the toxicity rate.

    Time frame: Up to 9 years

  5. Time to Next Therapy

    Estimated using the method of Kaplan and Meier.

    Time frame: Up to 4.5 years

07

Results

Posted Nov 4, 2020
Limitations and caveats
No pharmaco-dynamic marker to support an effect of signaling downregulation in lenalidomide-refractory patients to corroborate low dose thalidomide (50-100 mg) with or without dexamethasone has a therapeutic benefit with lenalidomide.

Participant flow

Participant flow — Overall Study
MilestoneRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Started33949
Phase 1 completed2360
Phase 2 completed00046
Completed23626
Not completed10323
Withdrew: Adverse event0012
Withdrew: Death0010
Withdrew: Withdrawal by subject1005
Withdrew: Disease progression00116

Outcome measures

PrimaryNumber of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

To determine the dose limitations toxicities of the combination of lenalidomide and thalidomide and dexamethasone (LTD) in patients with relapsed/refractory multiple myeloma (RRMM).

Time frame:
After one 28-day cycle
Reported as:
Count of participants · Participants
Number of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)
ParticipantsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Number of Participants With Dose Limitations Toxicities of the Combination of Lenalidomide and Thalidomide and Dexamethasone (LTD) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)1030
PrimaryComplete Response(CR) and Very Good Partial Response(VGPR)

To determine the best overall response (CR+VGPR+PR) of the lenalidomide, thalidomide, dexamethasone combination based on IMWG criteria at nadir.

Time frame:
Evaluated each 28-day cycle and nadir of criteria is considered best overall response (median time to best response for this study was 2 cycles (range for best overall response was 1-21 cycles).
Reported as:
Count of participants · Participants
Complete Response(CR) and Very Good Partial Response(VGPR)
ParticipantsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Partial Remission20213
Progressive Disease0226
Very Good Partial Remission0318
Minimal Residual Disease0019
Stringent Complete Remission0003
Non Evaluable1037
Stable Disease0007
SecondaryTime to Progression

Time to Progression was estimated using Kaplan Meier analysis.

Time frame:
Up to 9 years
Reported as:
Mean · Months
Time to Progression
MonthsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Time to Progression32.74 ± 279.04 ± 7.4914.61 ± 16.4110.02 ± 17.61
SecondaryProgression Free Survival

Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

Time frame:
Up to 9 years
Reported as:
Mean · Months
Progression Free Survival
MonthsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Progression Free Survival32.74 ± 279.04 ± 7.4914.61 ± 16.4110.02 ± 17.61
SecondaryTime to Best Response

Estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups was made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

Time frame:
Up to 9 years
Reported as:
Mean · months
Time to Best Response
monthsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Time to Best Response19 ± 1.415 ± 6.085.16 ± 7.033.3 ± 4.2
SecondaryIncidence of Adverse Events

Linear regression was utilized to assess the effect of patient prognostic factors on the toxicity rate.

Time frame:
Up to 9 years
Reported as:
Count of participants · Participants
Incidence of Adverse Events
ParticipantsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Incidence of Adverse Events00210
SecondaryTime to Next Therapy

Estimated using the method of Kaplan and Meier.

Time frame:
Up to 4.5 years
Reported as:
Median · months
Time to Next Therapy
monthsRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Time to Next Therapy52.4 (1.94 to NA)14.3 (5.19 to NA)10.5 (4.96 to NA)6.47 (4.14 to NA)

Adverse events

Collected over Baseline to study completion up to 9 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RTD (Cohort 1, Phase 1)0/3 (0%)0/3 (0%)3/3 (100%)
RTD (Cohort 2, Phase 1)0/3 (0%)0/3 (0%)3/3 (100%)
RTD (Cohort 3, Phase 1)1/9 (11.1%)1/9 (11.1%)9/9 (100%)
RTD (Cohort 2, Phase 2)0/49 (0%)7/49 (14.3%)49/49 (100%)
Most frequent serious events
Most frequent serious events
EventRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
DeathGeneral disorders0/30/31/90/49
PneumoniaRespiratory, thoracic and mediastinal disorders0/30/30/93/49
Altered Mental StatusPsychiatric disorders0/30/30/92/49
FatigueGeneral disorders0/30/30/91/49
Urinary Tract InfectionRenal and urinary disorders0/30/30/91/49
DiarrheaGastrointestinal disorders0/30/30/91/49
Abdominal PainGastrointestinal disorders0/30/30/91/49
Muscle WeaknessMusculoskeletal and connective tissue disorders0/30/30/91/49
VomitingGastrointestinal disorders0/30/30/91/49
Most frequent other events
Showing 10 of 164
Most frequent other events
EventRTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)
Activated PTTInvestigations1/33/37/912/49
HyperglycemiaInvestigations2/33/37/945/49
HypocaligulopathyInvestigations1/33/36/97/49
Edema LimbsGeneral disorders2/33/38/936/49
FatigueGeneral disorders1/33/39/949/49
AnemiaInvestigations3/31/36/943/49
ANC DecreaseInvestigations3/30/34/933/49
HypoalbumeniaInvestigations2/32/39/933/49
Metabolic/Laboratory (Other)Investigations2/31/38/929/49
HypocalcemiaInvestigations1/32/38/925/49

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
<=18 years00000
Between 18 and 65 years0212629
>=65 years3182335
Sex: Female, Male
Sex: Female, Male(Participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
Female1031923
Male2363041
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
Hispanic or Latino00033
Not Hispanic or Latino3394661
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
American Indian or Alaska Native00000
Asian00011
Native Hawaiian or Other Pacific Islander00000
Black or African American2241018
White1153845
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
United States3394964
Relapsed/Refractory Multiple Myeloma
Relapsed/Refractory Multiple Myeloma(Participants)RTD (Cohort 1, Phase 1)RTD (Cohort 2, Phase 1)RTD (Cohort 3, Phase 1)RTD (Cohort 2, Phase 2)Total
Age >= 18 years old3394964
> = 1 line of previous therapy3394964
Measurable levels of myeloma >=.5M serum-Protein2274455
Measurable levels of myeloma >=.2 Urine-Protein0174250
Abnormal Free Light Chain Ratio2394660
Creatine < 2.5 mg/dL3394964
Platelets > 50,0003394762
Total Bilirubin < 2.03394964
AST or ALT < 3x Upper Limit3394964
Anti-coagulant tolerance (PTT) normal2343746
Cognitively Aware & Physically Able2274556
No Pregnant/Breast Feeding Females1391932
Females non-procreative sex1391932
Men non-procreative sex2393044
No Cancer Therapy in 21 days3394964
No Desquamating Rash regarding Thalidomide3394964
Days off prev treatment >= 253394459
No Known Study Drug Allergies3394964
08

Study locations

1 site
  • M D Anderson Cancer Center
    Houston, Texas 77030, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Dec 12, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 4, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00966693
Lead sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 27, 2009
Start date
Aug 25, 2009
Primary completion
Jul 20, 2018
Completion
Jul 20, 2018
Results posted
Nov 4, 2020
Last update
Nov 4, 2020

Study contacts

Donna Weber
principal investigator · M.D. Anderson Cancer Center

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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