A Study of Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Patients With Relapsed/Refractory Myeloma With Salvage Autologous Hematopoietic Cell Transplantation

Study Purpose

The purpose of this study is to test any good and bad effects of giving a combination of study drugs before and after autologous stem cell transplant.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Patient must be capable, willing, and able to provide written, informed consent.
  • - Age ≥ 18-years-old and <= 75-years-old.
  • - Histologic confirmation of multiple myeloma by the enrolling institution.
  • - Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy.
  • - Patients who have received <=1 cycle of therapy after most recent progression/relapse are eligible to enroll on study.
  • - Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted.
  • - Bisphosphonates are permitted.
  • - Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted.
  • - Prior treatment with radiotherapy is permitted.
  • - Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 4 weeks from last dose (on a trial or outside a trial) are eligible.
  • - Maintenance single agent imid (ie. lenalidomide or pomalidomide) or monoclonal antibody (ie. daratumumab) do not require the 4-week washout period.
  • - More than 2 x 10^6 autologous CD34+ cells/kg cryopreserved.
The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center.
  • - Planning to receive autologous HCT per institutional standards as part of standard of care.
Eligibility for autologous HCT should be based on institutional guidelines.
  • - However, at minimum all patients must meet the following criteria: - KPS greater than 70.
  • - Cardiac left ventricular ejection fraction of greater than 40% - Calculated creatinine clearance of greater than 40 cc/min.
  • - AST and ALT of less than 2 x upper limit of normal.
  • - Direct bilirubin of less than 2 x upper limit of normal.
  • - Total bilirubin of less than 2 x upper limit of normal.
If Total bilirubin is abnormal. Direct bilirubin of less than 2 x upper limit of normal.
  • - Measurable disease as defined by any of the following International Myeloma Working Group Criteria.
  • - Monoclonal serum peak of greater than 0.5 gms per deciliter.
  • - Measurable urine peak as defined by urine protein electrophoresis of greater than 100 mg per 24 hours.
  • - Serum FLC assay: involved FLC level ≥10 mg/dL provided serum FLC ratio is abnormal.
  • - Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (subjects may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines) - Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to initial treatment (subjects may be receiving platelet transfusions in accordance with institutional guidelines) .
  • - Women of childbearing potential (WOCBP) † must agree to ongoing pregnancy testing and to practice contraception as described in section 9.3 and required by the Revlimid REMS program.
† A woman of childbearing potential is a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy or 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).
  • - Male subjects must agree to practice contraception.
  • - All study participants must be registered into the mandatory Revlimid REMS program and be willing and able to comply with the requirements of the REMS program.

Exclusion Criteria:

  • - Plasma cell leukemia (>20% circulating plasma cells) during screening studies.
  • - POEMS syndrome.
  • - Pregnant or lactating females.
Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study.
  • - Uncontrolled hypertension or diabetes.
  • - Active hepatitis B or C infection.
  • - Patients with HBV core antibody positive, but HBV PCR negative are eligible if they are on medication for suppression of HBV reactivation.
  • - Patients with HCV antibody positive, but PCR negative are eligible.
  • - Serologically positive HIV (testing required during screening) - Significant cardiovascular disease with NYHA Class III or IV symptoms, EF<40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination.
Echocardiogram will be performed during screening evaluation.
  • - Moderate or severe pulmonary hypertension defined as PASP >50 mm Hg.
  • - Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal.
Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is < 50% of predicted normal.
  • - Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
  • - Refractory GI disease that would prevent absorption of oral agents.
  • - Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements.
  • - Significant neuropathy ≥Grade 3 or Grade 2 neuropathy with pain at baseline.
  • - Contraindication to any concomitant medication, including antivirals or anticoagulation.
  • - Major surgery within 3 weeks prior to first dose.
  • - Prior Allogeneic HCT (prior autologous transplant is allowed regardless of response) - History of CNS involvement by myeloma.
  • - Disease progression as defined by IMW Criteria1 on the combination of carfilzomib, lenalidomide and dexamethasone (Patients with progression on lenalidomide maintenance after completion of carfilzomib, lenalidomide and dexamethasone combination therapy will be eligible).
  • - Disease progression on daratumumab.
  • - Prior dose limiting toxicity from carfilzomib or lenalidomide.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03556332
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Memorial Sloan Kettering Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Gunjan Shah, MD
Principal Investigator Affiliation Memorial Sloan Kettering Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Study Website: View Trial Website
Arms & Interventions

Arms

Experimental: Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.

Interventions

Drug: - Carfilzomib

Dara-CRd Induction Cycle 1 ONLY: Carfilzomib 20 mg/m2 per dose, days 1 and 2; Carfilzomib 27 mg/m2 per dose, days 8, 9, 15, and 16 Cycles 2-4: Carfilzomib 27 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16 Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Carfilzomib 27 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16

Drug: - Lenalidomide

Dara-CRd Induction Cycles 1-4: Lenalidomide 25 mg/day, days 1-21 every 28 days Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Lenalidomide 25 mg/day, days 1-21 every 28 days

Drug: - Dexamethasone

Dara-CRd Induction Cycles 1-4: Dexamethasone 20 mg/dose, days 1, 2, 8, 9, 15, 16, 22, 23 Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Dexamethasone 20 mg/dose, days 1, 2, 8, 9, 15, 16, 22, 23

Drug: - Daratumumab

Dara-CRd Induction Cycles 1 and 2: Daratumumab 16 mg/kg weekly (days 1,8, 15, 22) Dara-CRd Consolidation (60-90 days post HCT) Cycles 3 and 4: Daratumumab 16 mg/kg every other week, days 1 and 15. Cycles 5-6:Daratumumab 16 mg/kg every other week, days 1 and 15. Schedule together with Carfilzomib and use scheduled dexamethasone as premed. Cycles 7-8: Daratumumab 16 mg/kg days 1 of each cycle.

Procedure: - autologous hematopoietic cell transplantation

High Dose Melphalan and Autologous Hematopoietic Cell Transplantation Patients will receive Melphalan 200 mg/m2 per institutional guidelines, or if over 70 years of age or creatinine >2mg/dL, they will receive 140 mg/m2.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Birmingham, Alabama

Status

Recruiting

Address

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294

Site Contact

Susan Bal, MD

shahg@mskcc.org

205-801-9034

Memorial Sloan Kettering Basking Ridge, Basking Ridge, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Hackensack, New Jersey

Status

Not yet recruiting

Address

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601

Site Contact

Noa Biran, MD

shahg@mskcc.org

551-996-5900

Memoral Sloan Kettering Monmouth, Middletown, New Jersey

Status

Recruiting

Address

Memoral Sloan Kettering Monmouth

Middletown, New Jersey, 07748

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Memorial Sloan Kettering Bergen, Montvale, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Memorial Sloan Kettering Commack, Commack, New York

Status

Recruiting

Address

Memorial Sloan Kettering Commack

Commack, New York, 11725

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Memorial Sloan Kettering Westchester, Harrison, New York

Status

Recruiting

Address

Memorial Sloan Kettering Westchester

Harrison, New York, 10604

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Northwell Health, Manhasset, New York

Status

Recruiting

Address

Northwell Health

Manhasset, New York, 11030

Site Contact

Ruthee-lu Bayer, MD

shahg@mskcc.org

516-734-8973

New York University, New York, New York

Status

Recruiting

Address

New York University

New York, New York, 10010

Site Contact

Samer Al-Homsi, MD

shahg@mskcc.org

646-501-4848

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Site Contact

Gunjan Shah, MD, MS

shahg@mskcc.org

212-639-8356

Memorial Sloan Kettering Nassau, Uniondale, New York

Status

Recruiting

Address

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553

Site Contact

Gunjan Shah, MD

shahg@mskcc.org

212-639-8356

Wake Forest University, Winston-Salem, North Carolina

Status

Recruiting

Address

Wake Forest University

Winston-Salem, North Carolina, 27109

Site Contact

Cesar Rodriguez, MD

shahg@mskcc.org

336-713-5440

Medical College of Wisconsin, Milwaukee, Wisconsin

Status

Recruiting

Address

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Site Contact

Saurabh Chhabra, MD, MS

shahg@mskcc.org

414-805-0505