Clinical trial NCT01745588: Autologous Stem Cell Transplant With Pomalidomide (CC-4047®) Maintenance Versus Continuous Clarithromycin/ Pomalidomide / Dexamethasone Salvage Therapy in Relapsed or Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: CC-4047(Pomalidomide)Pomalyst
Clarithromycin
Biaxin
DEXAMETHASONE
(ClaPD)
Stem cell
12-138
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Weill Medical College of Cornell University
name: North Shore University Hospital
name: Rutgers Cancer Institute of New Jersey
name: State University of New York - Upstate Medical University
First posted: 2012-12-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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 active 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.

Primary outcomes:
measure: overall response rate
timeFrame: at 9 months after the start of treatment
Secondary outcomes:
measure: safety analyses
timeFrame: 3 years
measure: overall survival
timeFrame: 1 year
measure: progression free survival
timeFrame: 1 year
measure: Determine the rates of ≥ Grade 3 toxicities
timeFrame: 1 year
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering West Harrison
state: New York
city: New Hyde Park
country: United States
facility: North Shore LIJ
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Cancer Center at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Sergio Giralt, MD
role: PRINCIPAL_INVESTIGATOR
References: