Lenalidomide and Low-Dose Dexamethasone in Patients With Previously Treated Multiple Myeloma and Kidney Dysfunction (PrE1003)
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Purpose
Patients with previously treated multiple myeloma and kidney dysfunction will be treated with lenalidomide and low-dose dexamethasone. Phase I will study the side effects and best dose of lenalidomide when given together with low-dose dexamethasone therapy. After the maximum safe and tolerated dose is found in Phase I, the study will proceed to Phase II. Phase II will study how well the the treatment works in patients with previously treated (relapsed or refractory) multiple myeloma and kidney dysfunction.
Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone may kill more cancer cells. Lenalidomide and dexamethasone may have different effects in patients who have changes in their kidney function.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma Plasma Cell Neoplasm |
Drug: Group A=30-60 CrCl (mL/min) Drug: Group B=CrCL<30 mL/min not on dialysis Drug: Group C=CrCL<30 mL/min and on dialysis |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients With Impaired Renal Function |
- Maximum tolerated dose of lenalidomide (Phase I) [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]Phase I-Establish the maximum tolerated dose of lenalidomide in each of three groups of myeloma patients with impaired renal function.
- Assess response rate (Phase II) [ Time Frame: 56 months ] [ Designated as safety issue: No ]Phase II- Assess the efficacy (response rate [CR, sCR, VGPR, PR]) of this combination across the three groups of myeloma patients with impaired renal function.
- Survival time [ Time Frame: 56 months ] [ Designated as safety issue: No ]To describe the overall survival and progression-free survival of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.
- Duration of response [ Time Frame: 56 months ] [ Designated as safety issue: No ]To describe the duration of response and time to treatment failure of myeloma patients with impaired renal function treated with lenalidomide and dexamethasone.
- Safety profile [ Time Frame: 56 months ] [ Designated as safety issue: Yes ]To evaluate the safety profile of lenalidomide given in combination with weekly dexamethasone in myeloma patients with impaired renal function.
- Renal function over time [ Time Frame: 56 months ] [ Designated as safety issue: Yes ]To describe renal function over time and to evaluate the safety profile of a onetime increase in lenalidomide dose at least 2 cycles after start of treatment due to improved renal function.
- Pharmacokinetics of lenalidomide in impaired renal function [ Time Frame: 56 months ] [ Designated as safety issue: No ]To determine the pharmacokinetics of lenalidomide administration in myeloma patients with impaired renal function (pharmacokinetic analysis will be performed in up to 12 consented Mayo Clinic subjects treated during the Phase II component of the trial (only).
| Estimated Enrollment: | 111 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | January 2016 |
| Estimated Primary Completion Date: | October 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Group A=30-60 CrCl (mL/min)
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
|
Drug: Group A=30-60 CrCl (mL/min)
Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.
Other Names:
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Group B=CrCL<30 mL/min not on dialysis
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
|
Drug: Group B=CrCL<30 mL/min not on dialysis
Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.
Other Names:
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Group C=CrCL<30 mL/min and on dialysis
Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
|
Drug: Group C=CrCL<30 mL/min and on dialysis
Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II. Dialysis includes hemodialysis or peritoneal dialysis. When lenalidomide and/or dexamethasone treatment occurs on a dialysis day, lenalidomide and/or dexamethasone must be taken after dialysis. Other Names:
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Detailed Description:
Multiple Myeloma (MM) affects approximately 20,000 Americans annually and remains an incurable hematologic malignancy characterized by frequent early response followed by universal treatment relapse necessitating multiple sequential therapeutic regimens. Until recently, few effective therapies existed. Several novel agents for MM have now become available including the immunomodulatory drugs thalidomide, lenalidomide, as well as the proteasome inhibitor, bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Lenalidomide has proven to be a highly effective treatment agent, particularly when used in combination with dexamethasone but is renally excreted and little information is available about its use in myeloma patients with impaired kidney function (20% have renal failure at some time after diagnosis). Defining a safe and effective dose of lenalidomide to use is a critical step in MM treatment.
OUTLINE: This is a Phase I, dose-escalation study of lenalidomide followed by a Phase II study. Patients are stratified according to degree of renal dysfunction (moderate [creatinine clearance 30-60 mL/min] vs severe [creatinine clearance <30 mL/min and does not require dialysis] vs end-stage renal disease [creatinine clearance <30 mL/min and requires dialysis]).
Patients receive oral lenalidomide on days 1-21 and low-dose oral dexamethasone 40 mg on days 1, 8, 15, and 22. There is a 7 day rest (days 22-28) from lenalidomide. Each cycle is 28 days and repeated in the absence of disease progression or unacceptable toxicity.
Patients enrolled in the phase II portion of the study will undergo blood sample collection periodically for pharmacokinetic analysis of lenalidomide (Mayo Clinic sites only).
After completion of study treatment, patients are followed every 6 months for up to 3 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosed with previously treated multiple myeloma.
Measurable disease assessed by one of the following ≤21 days prior to registration:
- Serum monoclonal protein ≥1 g by protein electrophoresis
- Urine monoclonal protein >200 mg on 24 hour electrophoresis
- Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease)
- NOTE: If both serum and urine m-components are present, both must be followed in order to evaluate response.
- All previous cancer therapy including chemotherapy, radiation, hormonal therapy and surgery, must be discontinued ≥2 weeks prior to registration.
- Age ≥18 years.
- ECOG performance status 0-2.
Acceptable organ and marrow function ≤21 days prior to registration:
- ANC ≥1000/mm³
- Platelet count ≥75,000/mm³
- Total bilirubin ≤2 mg/dL
- AST and ALT ≤3 x upper limit of normal
- Renal impairment at baseline as measured by serum creatinine clearance (CrCl) ≤60 mL/min ≤21 days prior to registration.
- Females of Childbearing Potential (FCBP) must have a negative pregnancy test within 10-14 days and again within 24 hours of starting Cycle 1 and must use an effective double-method contraception for ≥28 days prior to, during, and for ≥28 days after completion of study therapy.
- Able to take required prophylactic anticoagulation.
- Able to understand and willingness to sign a written informed consent.
- Willing to provide blood samples for research purposes (Mayo Clinic sites only).
- If previously received lenalidomide, demonstration of clinical response of any duration or stable disease with progression-free interval of ≥6 months from start of that therapy.
Exclusion Criteria:
- Concurrent use of other anti-cancer agents or treatments. NOTE: Growth factors and bisphosphonates are allowed as medically indicated. Steroids may be used with an equivalency of up to 20 mg of Prednisone per day as long as the dose has not been adjusted upwards in past 2 weeks prior to study registration.
Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection requiring IV antibiotics
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Psychiatric illness/social situation that would limit compliance with study requirements.
Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Breast-feeding women
- Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception.
- HIV-positive patients on combination antiretroviral therapy.
- Known hypersensitivity to thalidomide or other immunomodulatory drugs.
- History of Stevens-Johnson syndrome characterized by a desquamating rash while taking thalidomide or similar drugs.
- Other active malignancy except for non melanoma skin cancer or in situ cervical or breast cancer.
- Concurrent radiation therapy, except for palliation of a single painful bone lesion or fracture.
Contacts and Locations| Contact: Carolyn Andrews, RN | 267-207-4070 | candrews@ecogchair.org |
| United States, Arizona | |
| Mayo Clinic in Arizona | Recruiting |
| Scottsdale, Arizona, United States, 85259-5499 | |
| Contact: Mayo Clinic Clinical Trials Office 507-538-7623 | |
| Principal Investigator: Joseph R. Mikhael, MD | |
| United States, Georgia | |
| Emory University Winship Cancer | Recruiting |
| Atlanta, Georgia, United States, 30322 | |
| Contact: Alaina R. Mitchell 404-778-5747 alaina.r.mitchell@emory.edu | |
| Contact: Jennifer Schreiber | |
| Principal Investigator: Jonathan Kaufman, MD | |
| United States, Illinois | |
| University of IL at Chicago | Recruiting |
| Chicago, Illinois, United States, 60612 | |
| Contact: Alisha Williams, RN 312-413-2746 alishaw@uic.edu | |
| Principal Investigator: David Peace, MD | |
| United States, Iowa | |
| McFarland Clinic | Recruiting |
| Ames, Iowa, United States, 50010 | |
| Contact: Janet Mannetter 515-239-2621 mannetter@mgmc.com | |
| Contact: Stephanie Greene, RN 515-956-2759 greene@mgmc.com | |
| Principal Investigator: Joseph Merchant, MD | |
| Siouxland Hematology Oncology Associates | Recruiting |
| Sioux City, Iowa, United States, 51101 | |
| Contact: Tom Hoopingarner 712-252-9326 shoaresearch@shoa-research.org | |
| Principal Investigator: Donald Wender, MD | |
| United States, Michigan | |
| Michigan Cancer Research Consortium and Oncology Research- St. Joseph Mercy Hospital - Ann Arbor | Recruiting |
| Ann Arbor, Michigan, United States, 48106-0955 | |
| Contact: Melissa Case 734-712-3621 casemr@trinity-health.org | |
| Contact: Lauren Swafford, R.N. 734-712-5674 swafforL@trinity-health.org | |
| Principal Investigator: Christopher Reynolds, MD | |
| Marquette General Hospital | Not yet recruiting |
| Marquette, Michigan, United States, 49855 | |
| Contact: Danielle Haanpaa 906-225-6995 danielle.haanpaa@mghs.org | |
| Principal Investigator: Amy Weise, MD | |
| United States, Minnesota | |
| Mayo Clinic | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Mayo Clinic Clinical Trials Office 507-538-7623 | |
| Principal Investigator: Suzanne R. Hayman, MD | |
| Metro MN CCOP | Recruiting |
| St. Louis Park, Minnesota, United States, 55416 | |
| Contact: Betsy Wagner 952-993-1555 elizabeth.wagner@parknicollet.com | |
| Principal Investigator: Jonathan Leach, MD | |
| United States, Nebraska | |
| Missouri Valley Cancer Consortium | Recruiting |
| Omaha, Nebraska, United States, 68106 | |
| Contact: Erin Smith 402-991-8070 ext 201 esmith@mvcc.cc | |
| Contact: Khaliq Nasrati 402-991-8070 ext 208 knasrati@mvcc.cc | |
| Principal Investigator: Gamini Soori, MD | |
| United States, New Jersey | |
| Hackensack University Medical Center | Recruiting |
| Hackensack, New Jersey, United States, 07601 | |
| Contact: Laura McBride, RN 201-996-5843 LMcBride@humed.com | |
| Contact: Palka Anand panand@humed.com | |
| Principal Investigator: David S. Siegel, MD | |
| United States, North Carolina | |
| Kinston Medical Specialists | Recruiting |
| Kinston, North Carolina, United States, 28501 | |
| Contact: Sheila Sutton, RHIA, CCRP 252-559-2201 Stsutton7@yahoo.com | |
| Contact: JoAnne Moye 252-559-2201 Jcmoye14@yahoo.com | |
| Principal Investigator: Peter R. Watson, MD | |
| United States, Pennsylvania | |
| University of Pennsylvania | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104-4283 | |
| Contact: Anita Reilly 215-615-3384 Anita.Reilly@uphs.upenn.edu | |
| Principal Investigator: Brendan Weiss, MD | |
| Reading Hospital and Medical Center | Recruiting |
| West Reading, Pennsylvania, United States, 19611 | |
| Contact: Serena Camlin, RN 610-988-5232 camlins@readinghospital.org | |
| Principal Investigator: Terrence Cescon, MD | |
| United States, West Virginia | |
| WVU Mary Babb Randolph Cancer Center | Recruiting |
| Morgantown, West Virginia, United States, 26506 | |
| Contact: Patricia Beal, RN, CRC 304-293-0609 pbeal@hsc.wvu.edu | |
| Principal Investigator: Mehdi Hamadani, MD | |
| United States, Wisconsin | |
| Gundersen Lutheran | Recruiting |
| La Crosse, Wisconsin, United States, 54601 | |
| Contact: Christine Meyer, CCRP 608-775-2837 cmmeyer2@gundluth.org | |
| Principal Investigator: Kurt Oettel, MD | |
| Waukesha Memorial Hospital (ProHealth Care) | Recruiting |
| Waukesha, Wisconsin, United States, 53188 | |
| Contact: Chanda Miller 262-928-5539 chanda.miller@phci.org | |
| Contact: Juli Hafeman juli.hafeman@phci.org | |
| Principal Investigator: Michael Thompson, MD | |
| Study Chair: | Joseph R. Mikhael, MD | Mayo Clinic |
More Information
Publications:
| Responsible Party: | PrECOG, LLC. |
| ClinicalTrials.gov Identifier: | NCT00790842 History of Changes |
| Other Study ID Numbers: | PrE1003, RV-MM-PrECOG-0394 |
| Study First Received: | November 13, 2008 |
| Last Updated: | May 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by PrECOG, LLC.:
|
Refractory Multiple Myeloma Relapsed Multiple Myeloma Multiple Myeloma with Renal Dysfunction |
Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma |
Additional relevant MeSH terms:
|
Plasmacytoma Neoplasms Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |
Dexamethasone acetate Dexamethasone Dexamethasone 21-phosphate Lenalidomide BB 1101 Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Gastrointestinal Agents Glucocorticoids |
ClinicalTrials.gov processed this record on May 21, 2013