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Evaluation of the Safety and the Efficacy of Carfilzomib Combined With Cyclophosphamide and Dexamethasone (CCyd) or Lenalidomide and Dex (CRd) Followed by ASCT or 12 Cycles of Carf Combined With Dex and Len for Patients Eligible for ASCT With Newly Diagnosed Multiple Myeloma. (FORTE)

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ClinicalTrials.gov Identifier: NCT02203643
Recruitment Status : Active, not recruiting
First Posted : July 30, 2014
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Silvio Aime, University of Turin, Italy

Brief Summary:

This study will evaluate the safety and the efficacy of carfilzomib combined with cyclophosphamide and dexamethasone (CCyd) or lenalidomide and dexamethasone (CRd) followed by autologous transplantation ASCT or 12 cycles of carfilzomib combined with dexamethasone and lenalidomide for patients eligible for ASCT with newly diagnosed multiple myeloma. As a secondary endpoint this study will evaluate the best maintenance treatment between lenalidomide and lenalidomide combined with carfilzomib.

Four hundred seventy-seven patients, males and females aged > 18 years, enrolled in several sites, will take part in this study.

The duration of the study is approximately 5 years.


Condition or disease Intervention/treatment Phase
MULTIPLE MYELOMA (MM) Drug: Carfilzomib Drug: Cyclophosphamide Drug: Lenalidomide Drug: Dexamethasone Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 477 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A MULTICENTER, RANDOMIZED, OPEN LABEL PHASE II STUDY OF CARFILZOMIB, CYCLOPHOSPHAMIDE AND DEXAMETHASONE (CCyd) as Pre Transplant INDUCTION and Post Transplant Consolidation or CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (CRd) as Pre Transplant INDUCTION and Post Transplant Consolidation or Continuous Treatment With CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (12 Cycles) Without Transplant, All Followed by MAINTENANCE With LENALIDOMIDE (R) Versus LENALIDOMIDE AND CARFILZOMIB (CR) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS ELEGIBLE FOR AUTOLOGOUS TRANSPLANT
Study Start Date : February 2015
Actual Primary Completion Date : October 2016
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: CCyd

Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.

After the end of consolidation all patients will be randomized to receive:

Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

Drug: Carfilzomib
Drug: Cyclophosphamide
Drug: Dexamethasone
Experimental: CRd

Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. This treatment will be followed by autologous stem cell transplantation (ASCT). Carfilzomib Cyclophosphamide and Dexamethasone administered for 4 28-day cycles, as consolidation treatment.

After the end of consolidation all patients will be randomized to receive:

Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

Drug: Carfilzomib
Drug: Lenalidomide
Other Name: Revlimid

Drug: Dexamethasone
Experimental: CRd long treatment

Carfilzomib Lenalidomide and Dexamethasone administered for 4 28-day cycles. Stem cells collection will be performed. Carfilzomib Lenalidomide and Dexamethasone administered for 8 28-day cycles.

After that all patients will be randomized to receive:

Lenalidomide or Lenalidomide and Carfilzomib until any sign of progression or intolerance.

Drug: Carfilzomib
Drug: Lenalidomide
Other Name: Revlimid

Drug: Dexamethasone



Primary Outcome Measures :
  1. Efficacy in term of at least Very Good Partial Response (VGPR) [ Time Frame: Up to 2 years ]
    The efficacy, in term of at least VGPR, of the combination of carfilzomib, dexamethasone with cyclophosphamide or lenalidomide after 4 cycles of induction treatment in newly diagnosed MM patients eligible for ASCT.


Secondary Outcome Measures :
  1. sCR rate [ Time Frame: up to 1 year ]
    the stringent complete response (sCR) rate in the 3 arms after complete primary therapy (induction, ASCT and consolidation for the transplant arms and after 12 cycles in the long treatment arm) in an explorative manner.

  2. Safety as incidence of grade 3/4 adverse events [ Time Frame: Up to 3 years ]
    the safety in the 3 induction/consolidation arms and in the 2 maintenance arms.

  3. Survival [ Time Frame: Up to 5 years ]
    the survival in the 3 induction/consolidation arms and in the 2 maintenance arms.

  4. Correlation between tumor response and outcome with baseline prognostic factors. [ Time Frame: up to 5 years ]
  5. Minimal Residual Disease (MRD) [ Time Frame: up to 5 years ]
    Minimal Residual Disease

  6. Survival after relapse [ Time Frame: up to 7 years ]
    the survival after relapse



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Age ≥ 18 years Newly diagnosed MM based on standard CRAB criteria (see appendix B). Patient < 65 years eligible for ASCT. Patient has measurable disease according to IMWG (International Myeloma Working Group) criteria.

Patient has given voluntary written informed consent. Patient agrees to use acceptable methods for contraception. Patient has a Karnofsky performance status ≥ 60%

Pretreatment clinical laboratory values within 30 days of enrolment:

Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is > 50%) Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors Corrected serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3 x the Upper Limit Normal (ULN) Total bilirubin: ≤ 2 x the ULN Calculated or measured creatinine clearance: ≥ 30 mL/minute. LVEF≥40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available Life expectancy ≥ 3 months

Exclusion Criteria:

Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days) Patients with non-secretory MM unless serum free-light chains are present and the ratio is abnormal or a plasmocytoma with minimum largest diameters of > 2 cm Patients ineligible for autologous transplantation Pregnant or lactating females

Presence of:

Clinical active infectious hepatitis type A, B, C or HIV Acute active infection requiring antibiotics or infiltrative pulmonary disease Myocardial infarction or unstable angina ≤ 4 months or other clinically significant heart disease Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 Known history of allergy to Captisol ® (a cyclodextrin derivative used to solubilize carfilzomib) Contraindication to any of the required drugs or supportive treatments Invasive malignancy within the past 3 years Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk.


Information from the National Library of Medicine

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): NCT02203643


Locations
Italy
IRCCS--CROB --CROB di Rionero in di Rionero in Vulture
Rionero in Vulture, Italy, 85028
Sponsors and Collaborators
Silvio Aime
Investigators
Principal Investigator: Antonio Palumbo, MD University of Turin, Italy

Responsible Party: Silvio Aime, MD, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT02203643     History of Changes
Other Study ID Numbers: UNITO-MM-01 / FORTE
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: September 6, 2017
Last Verified: September 2017

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
Lenalidomide
Cyclophosphamide
Thalidomide
BB 1101
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