Carfilzomib, Lenalidomide, and Dexamethasone Before and After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma
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| ClinicalTrials.gov Identifier: NCT01816971 |
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Recruitment Status : Unknown
Verified May 2017 by University of Chicago.
Recruitment status was: Active, not recruiting
First Posted : March 22, 2013
Last Update Posted : May 23, 2017
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma | Drug: dexamethasone Drug: carfilzomib Drug: lenalidomide Procedure: autologous hematopoietic stem cell transplantation Other: laboratory biomarker analysis | Phase 2 |
PRIMARY OBJECTIVES:
I. To determine the rate of stringent complete response (CR) (sCR) after 8 cycles of CRd (4 cycles of induction + autologous stem cell transplant [ASCT] + 4 cycles of carfilzomib, lenalidomide, and low dose dexamethasone [CRd] consolidation).
SECONDARY OBJECTIVES:
I. Overall response rate defined as partial response or better (>= partial response [PR]) including the rate of very good partial response (VGPR) or better (>= VGPR) and near complete response or better (sCR/CR/nCR) across entire treatment in high risk and low risk patients.
II. Duration of response (DOR), progression free survival (PFS), time to progression (TTP), and overall survival (OS).
TERTIARY OBJECTIVES:
I. Determination of the rate of minimal residual disease in patients who achieved CR.
II. Prospective evaluation of candidate markers of response to CRd established in the completed CRd trial.
III. Evaluation of markers of response and duration of response to treatment strategy using CRd with or without transplant.
OUTLINE:
INDUCTION THERAPY: Patients receive dexamethasone intravenously (IV) or orally (PO) once daily (QD) on days 1, 8, 15 and 22; carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16; and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity..
TRANSPLANT: Patients undergo autologous stem cell transplant.
CONSOLIDATION THERAPY: Patients receive dexamethasone, carfilzomib, and lenalidomide as in induction. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive dexamethasone and lenalidomide as in induction therapy and carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Treatment repeats every 28 days for 10 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 44 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Open-label, Single-arm, Phase 2 Study of the Initial and Post-Transplant Treatment With Carfilzomib, Lenalidomide and Low Dose Dexamethasone (CRd) in Transplant Candidates With Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy |
| Study Start Date : | January 2013 |
| Estimated Primary Completion Date : | April 2018 |
| Estimated Study Completion Date : | December 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Treatment (dexamethasone, carfilzomib, lenalidomide)
INDUCTION THERAPY: Patients receive dexamethasone IV or PO QD on days 1, 8, 15 and 22; carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16; and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.. TRANSPLANT: Patients undergo autologous stem cell transplant. CONSOLIDATION THERAPY: Patients receive dexamethasone, carfilzomib, and lenalidomide as in induction. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive dexamethasone and lenalidomide as in induction therapy and carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Treatment repeats every 28 days for 10 courses in the absence of disease progression or unacceptable toxicity. |
Drug: dexamethasone
Given IV or PO
Other Names:
Drug: carfilzomib Given IV
Other Names:
Drug: lenalidomide Given PO
Other Names:
Procedure: autologous hematopoietic stem cell transplantation Undergo autologous hematopoietic stem cell transplant Other: laboratory biomarker analysis Correlative studies |
- Proportion of patients achieving sCR [ Time Frame: Day 224 ]The proportion of sCR will be reported along with 95% confidence intervals, adjusted for the two-stage nature of the trial design.
- Overall response rate, defined as at least a partial response to therapy (> PR), at least VGPR and at least nCR rate [ Time Frame: Up to 2 years ]Reported along with its exact 95% binomial confidence interval.
- Time to progression [ Time Frame: Up to 2 years ]Estimated using the product-limit method of Kaplan and Meier.
- Duration of response [ Time Frame: Up to 2 years ]Reported along with its exact 95% binomial confidence interval. Estimated using the product-limit method of Kaplan and Meier.
- Progression-free survival [ Time Frame: Up to 2 years ]Estimated using the product-limit method of Kaplan and Meier.
- Overall survival [ Time Frame: Up to 2 years ]Estimated using the product-limit method of Kaplan and Meier.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Newly diagnosed, myeloma requiring systemic chemotherapy as per International Myeloma Working Group (IMWG) uniform criteria:
- Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids or lenalidomide or bortezomib-based regimens does not disqualify the patient (the treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle)
- Bisphosphonates are permitted
- Suitable and interested to proceed to ASCT
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Measurable disease, prior to initial treatment as indicated by one or more of the following:
- Serum monoclonal (M)-protein >= 0.5 g/dL
- Urine M-protein >= 200 mg/24 hours
- If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
- Life expectancy of more than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Bilirubin < 1.5 times the upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times ULN
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- Hemoglobin >= 8 g/dL
- Platelet count >= 75 x 10^9/L; subjects may receive red blood cell (RBC) transfusions or platelet transfusions, if clinically indicated in accordance with institutional guidelines; however, screening platelet count should be independent of platelet transfusions for at least 2 weeks
- Calculated or measured creatinine clearance of >= 50 mL/minute, calculated using the formula of Cockcroft and Gault
- Written informed consent in accordance with federal, local, and institutional guidelines
- Females of childbearing potential (FCBP) (defined as sexually mature females who: have not undergone a hysterectomy or bilateral oophorectomy; or have not been naturally postmenopausal for at least 24 consecutive months [ie, has had menses at any time in the preceding 24 consecutive months]) must agree to ongoing pregnancy testing
- FCBP must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide; the first pregnancy test must be performed within 10-14 days before day 1 cycle 1 and the second pregnancy test must be performed within 24 hours of day 1 cycle 1; the subject may not receive lenalidomide until the treating investigator has verified that the results of these pregnancy tests are negative, and must agree to ongoing pregnancy tests as outlined in the protocol
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FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study:
- For at least 28 days before starting lenalidomide
- While participating in the study; and
- For at least 28 days after discontinuation from the study; the 2 methods of reliable contraception must include a highly effective method (ie, intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and an additional effective (barrier) method (ie, latex condom, diaphragm, cervical cap); FCBP must be referred to a qualified provider of contraceptive methods if needed
- 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
- Male subjects must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant
- Male subjects must agree not to donate semen or sperm while taking lenalidomide
- All study participants must be registered into the mandatory Rev Assist program and be willing and able to comply with the requirements of Rev Assist
- The ability to take aspirin or other appropriate venous thromboembolism (VTE) prophylaxis
- Subjects must agree to adhere to all study requirements, including birth control measures and pregnancy testing, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring
Exclusion Criteria:
- Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as < 0.5 g/dL M-protein in serum, < 200 mg/24 hr urine M-protein, or disease only measured by serum free light chain
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Waldenstrom's macroglobulinemia or immunoglobin (Ig)M myeloma
- Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
- Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater
- Pregnant or lactating females
- History of allergy to mannitol
- Major surgery within 3 weeks prior to first dose
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Uncontrolled hypertension or diabetes
- Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Known or suspected human immunodeficiency virus (HIV) infection, known HIV seropositivity
- Active hepatitis A, B, or C infection
- Non-hematologic malignancy within the past 3 years except adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
- Any clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
- Significant neuropathy (grades 3-4, or grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment
- Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (eg, lansoprazole), enteric-coated aspirin, allopurinol or if a history of prior thrombotic disease, warfarin or low molecular weight heparin
- Subjects in whom the required program of PO and IV fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment
- Subjects with known or suspected amyloidosis of any organ
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
- No coverage or not-acceptable by patient co-pay for lenalidomide
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01816971
| United States, Illinois | |
| University of Chicago Comprehensive Cancer Center | |
| Chicago, Illinois, United States, 60637-1470 | |
| United States, Massachusetts | |
| Dana Farber | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Missouri | |
| Washington University in St Louis | |
| Saint Louis, Missouri, United States, 63130 | |
| United States, Tennessee | |
| Sarah Cannon Cancer Center | |
| Nashville, Tennessee, United States, 37203 | |
| Canada, Ontario | |
| Princess Margaret | |
| Toronto, Ontario, Canada, M5T 2M9 | |
| Principal Investigator: | Andrzej Jakubowiak | University of Chicago Comprehensive Cancer Center |
| Responsible Party: | University of Chicago |
| ClinicalTrials.gov Identifier: | NCT01816971 |
| Other Study ID Numbers: |
12-1725 NCI-2012-02023 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
| First Posted: | March 22, 2013 Key Record Dates |
| Last Update Posted: | May 23, 2017 |
| Last Verified: | May 2017 |
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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 Dexamethasone |
Lenalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors Angiogenesis Modulating Agents |