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A Study Of Daratumumab, Low-Dose Oral Dexamethasone and Cyclophosphamide With Or Without Pomalidomide (DCDP)

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ClinicalTrials.gov Identifier: NCT03215524
Recruitment Status : Recruiting
First Posted : July 12, 2017
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Myeloma Canada Research Network

Brief Summary:
This is a randomized phase II open label study of daratumumab, weekly low-dose oral cyclophosphamide and dexamethasone with or without pomalidomide in patients with relapsed and refractory multiple myeloma. The study consists of two arms. Patients will be randomized into ARM A and ARM B in a 1:1 ratio.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: DCdP Biological: DCd+P Phase 2

Detailed Description:

This is a randomized phase II open label study of daratumumab, weekly low-dose oral cyclophosphamide and dexamethasone with or without pomalidomide in patients with relapsed and refractory multiple myeloma. The study consists of two arms. Patients will be randomized into ARM A and ARM B in a 1:1 ratio.

In treatment ARM A patients will receive daratumumab, cyclophosphamide, dexamethasone and pomalidomide as per the following schedule:

  • Daratumumab, IV, at 16 mg/kg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.
  • Cyclophosphamide, orally, at 400 mg on Days 1, 8, 15 of each 28-day cycle. In order to prevent myelotoxicity and bladder toxicity, cyclophosphamide will be discontinued after cycle 24.
  • Dexamethasone orally at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40 mg dexamethasone weekly.
  • Pomalidomide, orally, at 4 mg on Days 1- 21 of each 28-day cycle.

In treatment ARM B, patients will receive daratumumab, cyclophosphamide, dexamethasone and pomalidomide as per the following schedule:

  • Daratumumab, IV, at 16 mg/kg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.
  • Cyclophosphamide, orally, at 400 mg on Days 1, 8 and 15 of each 28-day cycle. In order to prevent myelotoxicity and bladder toxicity, cyclophosphamide will be discontinued after cycle 24.
  • Dexamethasone at 20 mg orally on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40mg dexamethasone weekly.
  • Pomalidomide, orally, added at first progression at 4 mg on Days 1- 21 of each 28-day cycle.

Individual subjects will remain on treatment as long as there is no evidence of disease progression or unacceptable toxicity or patient/physician decision to discontinue. Disease assessment as determined by the Site Investigator will be made according to the IMWG response criteria guidelines for MM.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II, Open Label, Study of Daratumumab, Weekly Low-Dose Oral Dexamethasone and Cyclophosphamide With or Without Pomalidomide in Patients With Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : October 25, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : March 2023


Arm Intervention/treatment
Experimental: ARM A

Daratumumab, Cyclophosphamide, Dexamethasone, Pomalidomide

Daratumumab, IV, at 16 mg/kg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.

Cyclophosphamide, orally, at 400 mg on Days 1, 8, 15 of each 28-day cycle for 24 cycles.

Dexamethasone, orally, at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration, 40 mg dexamethasone weekly.

Pomalidomide, orally, at 4 mg on Days 1- 21 of each 28-day cycle.

Biological: DCdP
Daratumumab, Cyclophosphamide, Dexamethasone, Pomalidomide
Other Names:
  • Darzalex
  • Cytoxan
  • Pomalyst
  • Daratumumab
  • Cyclophosphamide
  • Pomalidomide
  • Dexamethasone

Experimental: ARM B

Daratumumab, Cyclophosphamide, Dexamethasone, Pomalidomide

Daratumumab, IV, at 16 mg/kg on days 1, 8, 15 and 22 for Cycles 1 and 2, on Days 1 and 15 for Cycles 3-6, and Day 1 of each cycle for Cycle 7 and beyond for each 28-day cycle.

Cyclophosphamide, orally, at 400 mg on Days 1, 8 and 15 of each 28-day cycle for 24 cycles.

Dexamethasone,orally, at 20 mg on day of daratumumab administration (pre-daratumumab) and 20 mg on the following day. On weeks without daratumumab administration,40mg dexamethasone weekly.

Pomalidomide, orally, added at first progression at 4 mg on Days 1- 21 of each 28-day cycle.

Biological: DCd+P
Daratumumab, Cyclophosphamide, Dexamethasone, + Pomalidomide added only at first confirmed biochemical progression
Other Names:
  • Darzalex
  • Cytoxan
  • Pomalyst
  • Daratumumab
  • Cyclophosphamide
  • Dexamethasone




Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: 36 months of from randomization ]
    Progression-free survival evaluation after 36 months



Information from the National Library of Medicine

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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 - Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

  1. Males or females, age 18 years or older.
  2. ECOG performance status score of 0, 1 or 2.
  3. Life expectancy of at least 3 months.
  4. Measurable disease according to the IMWG criteria defined as:

    1. Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E or M)
    2. Urine M-protein ≥ 200 mg/24 h
    3. Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an abnormal serum free light chain ratio (< 0.26 or > 1.65) if disease otherwise unmeasurable by a and b.
  5. Relapsed or relapsed and refractory disease defined as documented disease progression during or after completing their last treatment line and it must have contained either bortezomib and/or lenalidomide. The only exception for non-refractory patients is when re-treatment with these agents is medically contra-indicated.
  6. Have undergone at least 1 prior line of therapy. Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line.
  7. Have achieved at least a Minimal Response (MR) or better to at least one previous line of therapy.
  8. Have received at least 2 consecutive cycles of prior treatment that have included lenalidomide or bortezomib, either alone or in combination regimens, unless intolerant to these agents.
  9. Subjects must be eligible for pomalidomide reimbursement by their provincial jurisdictions or by the criteria of their insurance companies.
  10. Have the following laboratory values:

    1. ANC ≥ 1.0 x 109/L
    2. Hemoglobin ≥ 80 g/L
    3. Platelets ≥ 70 x 109/L (or ≥50 x 109/L if ≥50% plasmacytosis in bone marrow.
    4. Calculated CrCl ≥ 45 mL/min
    5. AST and ALT ≤ 3.0 x ULN
    6. Total bilirubin ≤ 2 x ULN unless known to have Gilbert's disease
    7. Corrected serum calcium ≤ 3.5 mmol/L
  11. Have signed the informed consent documents indicating that the subject understands the purpose of and procedures required for the study and is willing to participate and adhere to the study protocol.
  12. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of contraception* simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 90 days after study treatment discontinuation.

    †Females of childbearing potential (FCBP): a female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months).

    * The two methods of birth control used may be selected from the following categories, but the two methods cannot be selected from any one category: barrier method: i.e., condom (male or female) or diaphragm with spermicide; hormonal: i.e., contraceptive pill, patch; intrauterine device (IUD); vasectomy; or tubal ligation.

  13. Females must agree to abstain from breastfeeding during study participation and 90 days after study drug discontinuation.
  14. Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 90 days following discontinuation from this study, even if he has undergone a successful vasectomy.
  15. Males must also agree to refrain from donating semen or sperm during the treatment phase and for 90 days after discontinuation from this study treatment.
  16. All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment.
  17. All subjects must be eligible for enrollment and enrolled in the RevAid® program (refer to https://www.revaid.ca/revaid/ for RevAid eligibility).

Exclusion Criteria - Subjects who meet any of the following exclusion criteria are not eligible for enrollment:

  1. Prior exposure to daratumumab (or other anti-CD38 monoclonal antibody) or pomalidomide.
  2. History of prior allogeneic stem cell transplantation and showing evidence of active graft-versus-host disease or graft-versus-host disease that requires immunosuppressive therapy.
  3. Chemotherapy or other anti-myeloma therapy within 14 days prior to the first dose of study drug.
  4. Treatment-related toxicity that has not recovered ≤Grade 1 unless deemed to be irreversible (an example of an irreversible toxicity would include steroid induced cataracts). Peripheral neuropathy > Grade 2 or Grade 2 with pain will be excluded.
  5. Subjects who have received steroids within 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if subject receive ≤ 10 mg of prednisone per day, or equivalent, as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products prior to enrollment in this study.
  6. Subjects who have received any investigational agents within 28 days or 5 half-lives (whichever is longer) of the first dose (Cycle 1, Day 1).
  7. Prior history of malignancies, other than MM, unless the subject has been free of the disease for 3 years or longer. Exceptions include the following:

    1. Basal or squamous cell carcinoma of the skin,
    2. Carcinoma in situ of the cervix or breast,
    3. Adenocarcinoma of the prostate (TNM stage of T1a or T1b).
  8. Other concurrent severe and/or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol.
  9. Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 <50% predicted.
  10. Known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.
  11. History of or current uncontrolled cardiovascular disease including:

    1. Unstable angina, myocardial infarction, or known congestive heart failure Class III/IV (Appendix 5) within the preceding 12 months.
    2. Transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 months.
    3. Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy.
    4. QTc prolongation as confirmed by ECG assessment at screening (QTc >470 milliseconds).
  12. Women who are pregnant, breastfeeding or planning to become pregnant while enrolled in this study, or within 90 days after the last dose of study medications. Male subject who plans to father a child while enrolled in this study, within 90 days after the last dose of study medications.
  13. Known HIV positivity or active infectious hepatitis B or C.
  14. Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived products.
  15. Known CNS involvement, plasma cell leukemia or amyloidosis.
  16. Subjects who are receiving any other investigational agent.
  17. Autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug
  18. Any other condition that, in the Investigator's opinion, would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.

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): NCT03215524


Locations
Canada, Alberta
Tom Baker Cancer Centre Recruiting
Calgary, Alberta, Canada
Contact: Nizar Bahlis, MD    403-944-5246    nbahlis@ucalgary.ca   
CrossCancer Institute Recruiting
Edmonton, Alberta, Canada
Contact: Christopher Venner, MD    780-432-8757    christopherpaul.venner@albertahealthservices.ca   
Canada, British Columbia
Fraser Valley Cancer Centre Recruiting
Surrey, British Columbia, Canada
Contact: Jesse Shustik, MD    604-930-4064    jshustik@bccancer.bc.ca   
Canada, Manitoba
CancerCare Manitoba Recruiting
Winnipeg, Manitoba, Canada
Contact: Rami Kotb, MD    204-787-1036    rkotb@cancercare.mb.ca   
Canada, New Brunswick
Saint John Regional Hospital Recruiting
Saint John, New Brunswick, Canada
Contact: Anthony Reiman, MD    506-648-6884    anthony.reiman@horizonnb.ca   
Canada, Nova Scotia
QEII Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada
Contact: Darrell White, MD    902-473-4642    darrell.white@cdha.nshealth.ca   
Canada, Ontario
Juravinski Cancer Centre (Hamilton Health Sciences Centre) Recruiting
Hamilton, Ontario, Canada
Contact: Tom Kouroukis, MD    905-387-9495    kourouk@hhsc.ca   
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada
Contact: Andrea Kew, MD    613-737-8899 ext 71286    akew@toh.ca   
Thunder Bay Regional Health Sciences Centre Recruiting
Thunder Bay, Ontario, Canada
Contact: Nicole Laferriere, MD    807-684-7566    lafferin@tbh.net   
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada
Contact: Donna Reece, MD    416-946-2824    donna.reece@uhn.ca   
Canada, Saskatchewan
Saskatoon Cancer Centre Recruiting
Saskatoon, Saskatchewan, Canada
Contact: Julie Stakiw, MD    306-655-2980    julie.stakiw@saskcancer.ca   
Sponsors and Collaborators
Myeloma Canada Research Network

Responsible Party: Myeloma Canada Research Network
ClinicalTrials.gov Identifier: NCT03215524     History of Changes
Other Study ID Numbers: MCRN 004
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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
Pomalidomide
Daratumumab
Cyclophosphamide
Thalidomide
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones