Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study

Multiple Myeloma Clinical Trial

Official title:

Lenalidomide Plus Melphalan as a Preparative Regimen for Autologous Stem Cell Transplantation in Relapsed Multiple Myeloma: A Phase 1 / 2 Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01054196
• Other study ID #: 0909010623
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 2010
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A) Phase 1: To determine the maximal tolerated dose (MTD) of lenalidomide that can be safely added to high-dose melphalan prior to autologous stem cell transplantation (ASCT).

B) Phase 2: To determine whether the addition of high-dose lenalidomide to ASCT followed by maintenance standard-dose lenalidomide improves the response rate and duration of response for relapsed multiple myeloma (RMM).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed relapsed, primary refractory, or relapsed and refractory multiple myeloma.

• Patients must have measurable disease as defined by the International Uniform Response Criteria,defined as any of the following:

• serum M-protein of > = 500mg/dL

• urine M-protein of > = 200mg/ 24 hours

• involved free light chain > = 10mg/dL provided serum free light chain ratio is abnormal

• Patients must have received at least one prior line of therapy.

• Age > = 18 years.

• Life expectancy of greater than 12 weeks.

• ECOG performance status < = 2.

• All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.

• Patients must have normal organ and marrow function as defined below:

• ANC > = 1,000/uL

• platelets > = 50,000/uL

• total bilirubin < = 1.5 X upper limit of normal

• AST(SGOT)/ALT(SGPT) < = 2.5 X upper limit of normal

• Cardiac Ejection Fraction > = 45 %

• Creatinine clearance > 60 cc/min

• Patients must have an adequate number of CD34+ stem cells collected to allow for transplantation. This number is defined as = 2 x 106 CD34+ cells / kg body weight. If not previously collected and stored, the patient must be willing to undergo stem cell mobilization and collection as per standard practice.

• The effects of lenalidomide on the developing human fetus at the recommended therapeutic dose are unknown; however, it has been shown to be teratogenic other primates. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to 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 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 FCBP even if they have had a successful vasectomy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. The treating physician will follow the adverse reporting guidelines as outlined in further detail below for pregnancies.

• Lenalidomide has been shown to carry a risk of thromboembolic events, especially when used in combination with either corticosteroids or alkylating chemotherapeutic agents. All patients who participate in this study must be willing and able to tolerate prophylactic anticoagulation with low-molecular weight heparin (LMWH) for the required dates in treatment protocol. Patients also must be able to tolerate low-dose aspirin, 81 mg daily, during the maintenance phase of the treatment protocol.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients who have had myeloma therapy within 14 days prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Patients may have received bisphosphonate therapy as part of routine myeloma care at any time prior to study entry.

• Patients may not be receiving any other investigational agents.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide (including thalidomide) or melphalan.

• Known positive for HIV or infectious hepatitis, type B or C.

• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

• History of thrombosis or thromboembolic event within last 60 days prior to study entry.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• lenalidomide
daily dose dependent on dose-escalation schedule
• melphalan
100 mg/m2 given Days -2 and -1

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of lenalidomide that can be added to melphalan	The primary endpoint for the phase 1 portion of this study is to determine the maximum tolerated dose of lenalidomide that can be added to melphalan.	12 months
Primary	Duration of overall response (DoR)	The primary endpoint for the phase 2 portion of this study is to determine the duration of overall response (DoR). The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).	Until disease progression, death, or for a maximum of 3 years, whichever occurs first
Secondary	Overall Response Rate	Overall response rate is the number of patients with complete response and partial response. Response is defined by the International Uniform Response Criteria for Multiple Myeloma (IURC)	Until disease progression or a maximum of 3 years, whichever occurs first
Secondary	Overall Survival	Overall survival is defined as the interval between the day of transplantation (Day 0) and date of death. If the date of death is uncertain, the date of last contact with the subject will be used.	Until death or a maximum of 3 years, whichever occurs first
Secondary	Mean Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score	Quality of life will be evaluated and scored using the questionnaire from the bone marrow transplant subscale of the Functional Assessment of Cancer Therapy available from www.facit.org. The FACT-BMT is a 50 item questionnaire that measures five dimensions of quality of life in bone marrow transplant patients, including physical well-being, social and family well-being, emotional well-being, functional well-being, and additional concerns. It is scored on a 5 point Likert scale. Total scores range from 0 to 148, with a higher score indicating higher quality of life.	Cycle 6, day 1, at approximately 4.5 months

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