Autologous Stem Cell Transplant With Pomalidomide (CC-4047®) Maintenance Versus Continuous Clarithromycin/ Pomalidomide / Dexamethasone Salvage Therapy in Relapsed or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Celgene Corporation
Weill Medical College of Cornell University
North Shore University Hospital
Rutgers Cancer Institute of New Jersey
State University of New York - Upstate Medical University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01745588
First received: December 6, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to see whether pomalidomide (also known as Pomalyst) reduces the number of myeloma cells in the bones, and to see what is the best way to use pomalidomide in patients with myeloma. To do this, the investigators want to compare two types of treatment using pomalidomde. This is a randomized trial which means that the decision as to which treatment the patient will receive will be made by a computer, much like flipping a coin.

All patients start by receiving 4 cycles of clarithromycin, pomalidomide and dexamethasone (ClaPD). After 4 cycles, half of the patients will undergo an autologous stem cell transplant followed by pomalidomide (Group 1). The other half of the patients will continue to receive ClaPD for 9 cycles to be followed by pomalidomide maintenance. (Group 2).

At the end of the study, the two groups will be compared to see if there is a difference in disease outcome.


Condition Intervention Phase
Multiple Myeloma
Drug: Pomalidomide
Procedure: stem cell
Drug: Dexamethasone
Drug: Clarithromycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Stem Cell Transplant With Pomalidomide (CC-4047®) Maintenance Versus Continuous Clarithromycin/ Pomalidomide / Dexamethasone Salvage Therapy in Relapsed or Refractory Multiple Myeloma: A Phase 2 Open-Label Randomized Study by Tristate Consortium

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • overall response rate [ Time Frame: at 9 months after the start of treatment ] [ Designated as safety issue: No ]
    Very Good PR or greater will be evaluated nine months postrandomization according to International Uniform Response Criteria.


Secondary Outcome Measures:
  • safety analyses [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The frequency of subjects experiencing a specific adverse event will be tabulated overall and by each treatment course. In the by-subject analysis, a subject having the same event more than once will be counted only once. Adverse events will be summarized by worst NCI CTCAE grade. Laboratory data will be graded according to NCI CTCAE severity grade

  • overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • progression free survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Determine the rates of ≥ Grade 3 toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 as specified in section 10.0.


Estimated Enrollment: 44
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clarithromycin + Pomalidomide + Dexamethasone + stem cell
All patients will receive 4 cycles of clarithromycin 500mg twice daily on days 1-28, pomalidomide 4 mg daily on days 1 through 21 and dexamethasone orally at a dose of 40 mg daily on days 1, 8, 15, and 22 of each 28-day cycle. Patients randomized to auto-SCT will proceed within 28 days after completion of the 4th cycle of ClaPD to receive melphalan 200mg/m2 followed by hematopoietic cell infusion.
Drug: Pomalidomide Procedure: stem cell Drug: Clarithromycin
Experimental: Clarithromycin + Pomalidomide + Dexamethasone Alone
All patients will receive 4 cycles of clarithromycin 500mg twice daily on days 1-28 pomalidomide 4 mg daily on days 1 through 21 and dexamethasone orally at a dose of 40 mg daily on days 1, 8, 15, and 22 of each 28 day cycle. Patients assigned to ClaPD alone will receive 5 additional cycles of ClaPD.
Drug: Pomalidomide Drug: Dexamethasone Drug: Clarithromycin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed relapsed multiple myeloma as defined by the International Myeloma Working Group (IMWG).
  • 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 had a previous auto-SCT performed as part of a consolidation of an initial remission and had a remission, defined as a partial response or greater that lasted at least 12 months either on or off maintenance therapy without evidence of progression as defined by IMWG criteria.
  • Patients who are post auto-SCT as primary therapy must have received maintenance therapy with lenalidomide.
  • Patients must be registered within 6 months of last dose of lenalidomide.
  • Minimum of 3 months of maintenance therapy prior to disease progression.
  • Age ≥ 18 years.
  • Life expectancy of ≥12 weeks.
  • KPS ≥ 70 or ECOG < 1 (Appendix IV)
  • Patients must have adequate organ and marrow function as defined below:
  • ANC ≥ 750/μL
  • Platelets≥ 50,000/μL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST(SGOT) ≤ 3 X upper limit of normal.
  • ALT(SGPT) ≤ 3 X upper limit of normal.
  • Cardiac Ejection Fraction ≥ 40%
  • Serum Creatinine ≤ 2.0 mg/dL
  • Patients must have an adequate number of CD34+ stem cells collected to allow for transplantation (defined as ≥ 2x10^6 CD34+ cells / kg body weight). If not previously collected and stored or if previous collection was inadequate, the patient must be willing to undergo stem cell mobilization and collection as per standard practice.
  • Patients who participate in this study must be willing and able to tolerate prophylactic anticoagulation either with aspirin, low-molecular weight heparin (LMWH), or warfarin.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Patient must be determined fit to undergo auto-SCT procedure by a study physician.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS™ program. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing pomalidomide (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 pomalidomide. 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. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

    • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).
  • All study participants must be registered into the mandatory POMALYST REMS™ program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.

    • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).

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 or radiation therapy as part of routine myeloma care at any time prior to study entry.
  • Patients may not be receiving any other investigational agents.
  • Any prior use of thalidomide or pomalidomide.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide (including thalidomide) clarithromycin, or melphalan.
  • Known prior positivity 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 30 days prior to study entry.
  • Patients with CNS involvement.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745588

Contacts
Contact: Sergio Giralt, MD 212-639-6009
Contact: Hani Hassoun, MD 212-639-3228

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Sergio Giralt, MD    212-639-6009      
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Clinical Trials Office - Cancer Institute of New Jersey    732-235-8675      
Principal Investigator: Mecide Gharibo, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Sergio Giralt, MD    212-639-6009      
North Shore LIJ Recruiting
New Hyde Park, New York, United States, 11040
Contact: Ruthee-Lu Bayer, MD         
Principal Investigator: Ruthee-Lu Bayer, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sergio Giralt, MD    212-639-6009      
Contact: Hani Hassoun,, MD    212-639-3228      
Principal Investigator: Sergio Giralt, MD         
Weill Medical College of Cornell University Recruiting
New York, New York, United States
Contact: Tomer Mark, MD         
Principal Investigator: Tomer Mark, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Sergio Giralt, MD    212-639-6009      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Sergio Giralt, MD    212-639-6009      
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States
Principal Investigator: Teresa Gentile, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Celgene Corporation
Weill Medical College of Cornell University
North Shore University Hospital
Rutgers Cancer Institute of New Jersey
State University of New York - Upstate Medical University
Investigators
Principal Investigator: Sergio Giralt, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01745588     History of Changes
Other Study ID Numbers: 12-138
Study First Received: December 6, 2012
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CC-4047(Pomalidomide)Pomalyst
Clarithromycin
Biaxin
DEXAMETHASONE
(ClaPD)
Stem cell
12-138

Additional relevant MeSH terms:
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 acetate
Dexamethasone
Dexamethasone 21-phosphate
Thalidomide
BB 1101
Clarithromycin
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 July 20, 2014