Cyclophosphamide With Biochemical Progression During Lenalidomide-Dexamethasone Treatment for Relapsed/Refractory Multiple Myeloma (MM)

NCT02206503 | Completed Phase 2 DMC

• 1 other identifier: CRd
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the efficacy of the addiction of Cyclophosphamide to Revlimid-low dose dexamethasone (Rd) in relapsed/refractory Multiple Myeloma patients, who experienced a biochemical progression, without CRAB, during Rd treatment.

Conditions

Multiple Myeloma

Keywords

LENALIDOMIDE; BIOCHEMICAL PROGRESSION; RELAPSED/REFRACTORY MM; WITHOUT CRAB

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of response and survival

  To assess the efficacy (response rate according to International Myeloma Working Group (IMWG) definition, appendix 2) after the addiction of Cyclophosphamide to Revlimid-Dexamethasone (CRd) in Multiple Myeloma patients, who experienced a biochemical progression during Rd treatment, without myeloma-related organ damage, CRAB.

  2 years

Secondary Outcomes (6)

• Safety in terms of hematological and non-hematological adverse events

  2 years

• The progression free survival (PFS)

  2 years

• The overall survival (OS)

  2 years

• Duration of time to progression (TTP)

  2 years

• Time to next therapy (TNT)

  2 years

Study Arms (1)

Cyclophosphamide; Lenalidomide; Dexamethasone

EXPERIMENTAL

MM Patients who experienced biochemical progression during Rd treatment without CRAB (signs of organ damage, multiple myeloma-related, as renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia), will continue: * Lenalidomide orally at the dose of 25 mg/day for 21 days every 28 days. * Dexamethasone orally at the dose of 40 mg once a week. Adding: · Cyclophosphamide orally at the dose of 50 mg/day on days 1-21 every 28 days. CRd combination will be continued for 9-4week cycles. Patients will not receive any maintenance therapy.

Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Cyclophosphamide DRUG

This protocol is a phase II multicenter, open label study designed to determine whether the addition of Cyclophosphamide to Rd (CRd) treatment significantly increases response rates and prolonged the outcome (PFS, OS) in patients who experienced a biochemical relapse, without CRAB under Rd treatment. The treatment period includes: administration of the combination CRd for 9 cycles. In order to assess the efficacy and safety of treatment, patients will attend the study center visits at least every 2 weeks. The response will be assessed after each cycle. During the LTFU period, after development of confirmed PD, all patients are to be followed for survival every 1-3 months via telephone or office visit.

Cyclophosphamide; Lenalidomide; Dexamethasone

Lenalidomide DRUG

Cyclophosphamide; Lenalidomide; Dexamethasone

Dexamethasone DRUG

Cyclophosphamide; Lenalidomide; Dexamethasone

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with relapse/refractory multiple myeloma who experienced biochemical progression, without CRAB, during treatment with Rd. CRAB means the presence of organ damage, multiple myeloma related (renal impairment and/or anemia and/or new bone lesions and/or hypercalcemia). It is sufficient one of the previous signs for defining the presence of CRAB. Biochemical progression means: positivization of serum/urine immunofixation for patients who reached a complete remission with Rd treatment or at least 25% increment of monoclonal component in serum/urine for patients who reached at least a stable disease (SD).
• Patient exposed to previous therapy included Lenalidomide, Thalidomide, Bortezomib and/or autologous stem cell transplantation (ASCT) and in treatment with Rd.
• Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
• Female patient is either post-menopausal or surgically sterilized or, if at childbearing potential, must: understand that the study medication could have an expected teratogenic risk.
• Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception\*:
• Implant\*\*
• Levonorgestrel-releasing intrauterine system (IUS)\*\*
• Medroxyprogesterone acetate depot
• Tubal sterilisation
• Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
• Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
• Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of venous thromboembolism (VTE) continues for 4 to 6 weeks after stopping combined oral contraception.
• \*\*prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection.
• Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mills International Units on milliliter (mIU/ml) not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.

You may not qualify if:

• Patients with newly diagnosed multiple myeloma.
• Patients who relapsed from multiple myeloma with signs of organ damage related to disease (CRAB).
• Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
• Pregnant or lactating females.
• Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer (TNM stage of T1a or T1b).

Sponsors & Collaborators

• Fondazione EMN Italy Onlus: lead

Study Sites (1)

Policlinico Umberto I

Rome, 00161, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Cyclophosphamide; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Maria Teresa Petrucci, MD

  Policlinico Umberto I

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: August 1, 2014
• Study Start: March 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: July 1, 2018
• Last Updated: August 2, 2018

Record last verified: 2018-08

Locations

IT (1)