Dalteparin, Lenalidomide, and Low-Dose Dexamethasone in Treating Patients With Previously Untreated Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Southern California
Sponsor:
Collaborators:
Celgene Corporation
Information provided by (Responsible Party):
University of Southern California
ClinicalTrials.gov Identifier:
NCT01518465
First received: January 18, 2012
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

This randomized pilot phase II trial studies how well giving dalteparin, lenalidomide, and low-dose dexamethasone together works in treating patients with previously untreated multiple myeloma. Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients being treated with lenalidomide and dexamethasone for multiple myeloma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dalteparin, lenalidomide, and dexamethasone together may be an effective treatment for multiple myeloma


Condition Intervention Phase
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: dalteparin
Drug: lenalidomide
Drug: dexamethasone
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Lenalidomide and Low-dose Dexamethasone in Combination With Dalteparin in Previously Untreated Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Number of patients who experienced grade 4 hemorrhage regardless of attribution, or grade 3 hemorrhage that is possibly, probably, or definitely attributable to dalteparin (Arm II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Possible markers of anti-MM effect [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
  • Toxicities observed at each dose level, in terms of type (organ affected, laboratory determination), severity (by Common Toxicity Criteria [CTC]), time of onset, duration, and reversibility or outcome [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Overall response (CR+PR) calculated for each dose level separately [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Anti-thrombotic (syndecan-1, TAT, D-dimer, P-selectin) and anti-myeloma (M-spike and IL-6) marker levels [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: January 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (5000 IU dalteparin)
Patients receive a prophylactic dose of dalteparin SC on days 1-28; lenalidomide PO on days 1-21; and low-dose dexamethasone PO on days 1, 8, 15, and 22.
Drug: dalteparin
Given SC
Other Names:
  • DAL
  • dalteparin sodium
  • Fragmin
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (200 IU/kg dalteparin)
Patients receive a therapeutic dose of dalteparin SC on days 1-21 and lenalidomide PO and low-dose dexamethasone PO as in Arm I.
Drug: dalteparin
Given SC
Other Names:
  • DAL
  • dalteparin sodium
  • Fragmin
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: dexamethasone
Given PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To select a dose of Dalteparin to be used with Lenalidomide and low-dose dexamethasone in future trials for patients with previously untreated multiple myeloma (MM), based on toxicity, selected biomarkers (M-spike, interleukin [IL]-6) related to response and other markers of coagulation.

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (ORR = complete response [CR] + partial response [PR]), and time to progression (TTP) for this regimen at each of the two Dalteparin doses.

II. To evaluate the safety profile of this regimen in untreated MM patients, at each of the two Dalteparin doses.

III. To study the effect of Dalteparin alone, and in combination with lenalidomide/dexamethasone on serum biomarkers of multiple myeloma (MM) and thrombosis.

IV. To explore possible associations between the ORR and incidence of venous thromboembolism (VTE) with serial syndecan-1, IL-6, tyrosine aminotransferase (TAT), D-dimer, P-selectin levels.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive a prophylactic dose of dalteparin subcutaneously (SC) on days 1-28; lenalidomide orally (PO) on days 1-21; and low-dose dexamethasone PO on days 1, 8, 15, and 22.

ARM II: Patients receive a therapeutic dose of dalteparin SC on days 1-21 and lenalidomide PO and low-dose dexamethasone PO as in Arm I.

In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with residual responding disease may receive 2 additional courses. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

  Eligibility

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

Inclusion Criteria:

  • Patients must have a diagnosis of active MM requiring treatment, as diagnosed by a bone marrow biopsy within 8 weeks prior to study enrollment
  • Patients must not have received any previous treatment for MM (localized radiation therapy or single agent pulse steroid therapy for acute MM crises is permitted)
  • Life expectancy of greater than 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky >= 50%)
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Transaminases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) < 2.5 x ULN
  • Alkaline phosphatase < 2.5 ULN
  • Platelets >= 75,000 cells/mm3
  • Hemoglobin >= 8.0 g/dL
  • Absolute neutrophil count (ANC) > 1,000 cells/mm3 NOTE: Patients with platelet count < 75,000 or hemoglobin < 8.0 g/dl,or ANC <1,000 cell/mm3 secondary to extensive bone marrow disease can be enrolled at Principal Investigator's (PI) discretion with appropriate transfusion and/or cytokine support
  • Creatinine =< 2.5 mg/dL (=< 200 mmol/L) or creatinine clearance > 30 ml/min (as calculated by the Cockcroft-Gault formula)
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 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 lenalidomide; 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 study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
  • Willingness and ability to sign informed consent for the clinical trial

Exclusion Criteria:

  • Patients who have had any prior chemotherapy for MM; with the exception of pulse steroids for any myeloma-related acute events
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational
  • Pregnant or lactating women
  • Active serious infections uncontrolled by antibiotics at the time of treatment initiation
  • Inability to give 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 subject at any time without prejudice to future medical care
  • Failure to comply with birth control methods as described above
  • Any serious medical or psychiatric condition or reason that, in the PI's opinion, makes the patient unsuitable to participate in this clinical trial
  • Known to be human immunodeficiency virus (HIV) positive (if the status of HIV is not known and patient is not at risk, as determined by the PI, then the patient will not be specifically tested for HIV); HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with lenalidomide and/or dalteparin. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer (organ-confined, early stage disease) after curative therapy
  • Patients with M protein >6 gm/dl prior to starting treatment will be excluded from the initial "run-in" cohort on both arms of the study, but will be eligible for the subsequent enrollment of patients who do not have a run-in phase with dalteparin
  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: NCT01518465

Locations
United States, California
USC/Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Christine Duran    323-865-0371    Christine.Duran@med.usc.edu   
Principal Investigator: Ann Mohrbacher, MD         
Sponsors and Collaborators
University of Southern California
Celgene Corporation
Investigators
Principal Investigator: Ann Mohrbacher, MD University of Southern California
  More Information

No publications provided

Responsible Party: University of Southern California
ClinicalTrials.gov Identifier: NCT01518465     History of Changes
Other Study ID Numbers: 16M-11-1, NCI-2011-03784
Study First Received: January 18, 2012
Last Updated: March 3, 2014
Health Authority: United States: Federal Government

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
Lenalidomide
Thalidomide
BB 1101
Dalteparin
Heparin, Low-Molecular-Weight
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 23, 2014