Lenalidomide and High-Dose Melphalan

NCT01079936 | Completed Phase 1 Results DMC

• 2 other identifiers: 2008-0661NCI-2011-00561
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of Revlimid (lenalidomide) and high-dose Alkeran (melphalan) that can be given to patients with multiple myeloma who will receive an autologous stem cell transplantation. The safety of this combination therapy will also be studied.

Conditions

Myeloma; Stem Cell Transplantation

Keywords

Multiple Myeloma; Lenalidomide; Revlimid; Melphalan; Alkeran; Autologous stem cell transplantation; High-dose chemotherapy

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) of Lenalidomide

  There were 4 doses of lenalidomide in the dose escalation phase: 25 mg, 50 mg, 75 mg, and 100 mg. The first 12 patients were treated at these dose levels (3 patients per level) and safety assessed at each level. The MTD dose level was to be the level at which participants at each lenalidomide dose level had no dose limiting toxicity (DLT). DLT defined as as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT. Each participant received a fixed dose of Melphalan plus one of the four doses 25, 50, 75 or 100 mg of Lenalidomide orally for each of 7 days, -8 to -2 pre transplant.

  Assessed at 21-28 Day Cycle

• Number of Participants With Response (CR at Day 90)

  Response is defined as the event that the participant is alive with complete response (CR) at day 90 (+/-30 days). CR defined as: A) Absence of monoclonal protein in urine and serum when analyzed by immunofixation electrophoresis. B) The bone marrow should be normal by morphological examination with \<5% plasma cells. There should be \< 1% aneuploid light chain restricted population by flow cytometry for DNA/cIg. C) While healing of bone lesions not required, no new lytic lesion should appear. Further compression fracture of spine will be not considered as progressive disease.

  Day 90 after stem cell transplant

• Number of Participants With Day 30 DLT (Overall Study, Phase I/Phase II)

  Dose limiting toxicity (DLT) was defined as regimen-related death, graft failure, grade 3 or 4 atrial fibrillation, grade 4 deep venous thrombosis, or pulmonary embolism before day 30 after auto-HCT.

  Day 30 following transplant

• Participants With Grade 3 =/> Adverse Events

  Number of participants experiencing adverse events above a Grade 3 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.

  Day 90 after stem cell transplant

Study Arms (1)

Lenalidomide + High-Dose Melphalan

EXPERIMENTAL

Lenalidomide beginning dose level 25 mg by mouth (PO) on Days -8 to -2. High-Dose Melphalan dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion. Stem cell infusion on Day 0.

Drug: Lenalidomide; Drug: Melphalan; Procedure: Stem Cell Infusion

Interventions

Lenalidomide DRUG

Beginning dose level 25 mg by mouth (PO) on Days -8 to -2

Also known as: Revlimid, CC-5013

Lenalidomide + High-Dose Melphalan

Melphalan DRUG

Dose level 100 mg/m2 by vein (IV) Days -3 and -2 over 30 minutes infusion

Also known as: Alkeran

Lenalidomide + High-Dose Melphalan

Stem Cell Infusion PROCEDURE

Stem cell infusion on Day 0.

Lenalidomide + High-Dose Melphalan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with multiple myeloma with relapsed or progressive disease after achieving a partial or complete response to prior conventional therapy or autologous stem cell transplantation
• Age 18 to 80 years
• Performance score of at least 80% by Karnofsky or performance score of 0 or 1 (ECOG)
• Left ventricular ejection fraction =/\> 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
• FEV1, FVC and DLCO=/\> 40%. No symptomatic pulmonary disease.
• Serum bilirubin \<2 x upper limit of normal, SGPT \<3x upper limit of normal. No evidence of chronic active hepatitis or cirrhosis. No pleural effusion or ascites \> 1 L prior to drainage.
• Creatinine Clearance =/\> 50 ml/min
• HIV negative
• Negative beta HCG test in women with child bearing potential, defined as not post-menopausal for 24 months or no previous sterilization.
• Patients or guardian able to sign informed consent.
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 -14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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.
• Contd. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. See Appendix F: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

You may not qualify if:

• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
• Patients with uncontrolled hypertension (systolic \> 140, diastolic \>90 despite anti-hypertensive therapy.)
• Patients with uncontrolled bacteria, viral or fungal infections (currently taking medication and progression of clinical symptoms).
• Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide.
• Women who are pregnant (positive ß-HCG) or breastfeeding. (Lactating women must agree not to breast feed while taking lenalidomide and for 28 days after last dose of lenalidomide.)
• New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia's, or electrocardiographic evidence of acute ischemia, or a 2nd or 3rd degree AV block or new left bundle branch block on EKG.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

Lenalidomide; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Muzaffar H. Qazilbash, Professor, Stem Cell Transplantation
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Muzaffar H. Qazilbash, MD

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2010
• First Posted: March 3, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 6, 2016
• Results First Posted: June 6, 2016

Record last verified: 2016-05

Locations

US (1)