Cyclophosphamide(Cy)/ Dexamethasone(Dex)/Rapamycin (Rapa)/Hydroxychloroquine (HCQ) for Relapsed or Refractory Myeloma(Rel/Ref MM)

This study is currently recruiting participants.
Verified August 2013 by OHSU Knight Cancer Institute
Sponsor:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01689987
First received: September 17, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

Multiple myeloma (MM) is a type of cancer with an average survival of 3 to 5 years. The disease remains incurable and patients become unresponsive to treatments. Patients also develop organ problems and can have severe side effects from therapy. All of these factors limit treatment options. This protocol will enroll subjects who have MM that has returned after treatment or has stopped responding to treatment. The purpose of this study is to test the safety of rapamycin and hydroxychloroquine (study drugs) at different dose levels. The investigators want to find out what effects, good and/or bad, it has on MM. The study drugs have not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agency for general use in this type of cancer and their benefits and side effects are not fully known. These study drugs will be given with standard chemotherapy, cyclophosphamide and dexamethasone, which have both been approved by the FDA for use in this disease. The investigators believe that the combination of standard chemotherapy, with rapamycin and hydroxychloroquine (HCQ), may improve the response outcome compared to standard chemotherapy alone. The investigators think that both study drugs will improve the sensitivity of the myeloma cells in the body to standard chemotherapy, making it easier for the chemotherapy to kill or damage the myeloma cells. However, this combination has never been tried in patients before. In future research studies, the investigators hope to determine how well this drug combination will work in fighting and killing myeloma cells.


Condition Intervention Phase
Multiple Myeloma
Drug: Hydroxychloroquine
Drug: Rapamycin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase I Infusional Cyclophosphamide and Pulse Dexamethasone With Rapamycin and Hydroxychloroquine in Patients With Relapsed or Refactory Myeloma

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD)of Hydroxychloroquine (HCQ),Rapamycin, Dexamethasone, and Cyclophosphamide. [ Time Frame: Duration of the study; up to 2 years ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination with rapamycin and infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/ refractory multiple myeloma.


Secondary Outcome Measures:
  • Evaluation of biological activity [ Time Frame: Duration of the study; Up to 2 years ] [ Designated as safety issue: Yes ]
    To evaluate biological activity of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/ refractory multiple myeloma.

  • Evaluation of efficacy [ Time Frame: Duration of the study; up to 2 years ] [ Designated as safety issue: No ]
    To evaluate efficacy of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/ refractory multiple myeloma.


Estimated Enrollment: 18
Study Start Date: December 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydroxychloroquine/Rapamycin

Hydroxychloroquine (HCQ) oral will begin on day 5 of cycle 1 and daily thereafter. It will be given every day of all subsequent cycles (to be given with milk or food at approximately the same time each day, suggested with dinner at 4-6pm).

starting dose of HCQ (dose level 1) will be 400mg escalating as follows: 600mg, 800mg, on to the highest dose of 1200mg daily (dose level 4).

Rapamycin loading dose on day -2 of each cycle, followed by a daily dose on days -1 through 4 (on an empty stomach at approximately the same time every day- suggested at 2pm).

4mg rapamycin daily with 12mg loading dose

Drug: Hydroxychloroquine Drug: Rapamycin

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed multiple myeloma
  • Documented relapse or persistent disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)
  • Need for further treatment for myeloma, as determined by the patient's treating physician*
  • Age ≥18 years. Both men and women and members of all races and ethnic groups will be included.
  • ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix).
  • Ability to understand and the willingness to sign a written informed consent document.
  • Birth control is required with full barrier contraceptives or complete abstinence for the duration of time receiving therapy and for 6 months after completing the last drug taken.

    • The need for further treatment: This is defined as progression of clinical features (worsening anemia, renal function, bone disease, hypercalcemia, recurrent infections, and constitutional symptoms) or biochemical progression (increasing M-spike in serum or urine, involved serum or urine free light chain over 2 consecutive time points greater than 4 weeks apart).

Exclusion Criteria:

  • History of allergic reactions to compounds of similar chemical or biological composition to rapamycin or hydroxychloroquine
  • Patients may not take any of the following medications while on study, but will be considered eligible if medication is discontinued at least 72 hrs prior to first dose of Rapamycin.

    • Carbamazepine (e.g. Tegretol)
    • Rifabutin (e.g. Mycobutin)
    • Rifampin (e.g. Rifadin)
    • Rifapentine (e.g. Priftin)
    • St. John's Wort
    • Clarithromycin (e.g. Biaxin)
    • Cyclosporin e.g. (Neoral or Sandimmune)
    • Diltiazem (e.g. Cardizem)
    • Erythromycin (e.g. Akne-Mycin, Ery-Tab)
    • Itraconazole (e.g. Sporanox)
    • Fluconazole (e.g. Diflucan)
    • Ketoconazole (e.g. Nizoral)
    • Telithromycin (e.g. Ketek)
    • Verapamil (e.g. Calan SR, Isoptin, Verelan)
    • Voriconazole (e.g. VFEND)Tacrolimus (e.g. Prograf)
  • Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis (well-controlled psoriasis allowed provided under the care of a specialist who agrees to monitor the patient for exacerbations)
  • Patients with the following cytopenias:

    • ANC <1.0 x 109/L;
    • Platelets < 50 x 109/L for any reason
  • Patients with the following chemistry abnormalities:

    • Serum Creatinine > 2.5 mg/dL;
    • Total or Direct Bilirubin > 2.0 mg/dL;
    • Transaminases 2 x the upper limit of normal
    • Fasting Glucose > 200mg/dL
    • Serum potassium < 3.4 mmol/l
    • Serum phosphorus < 2.4mg/dl
  • Other conditions that would require therapy with hydroxychloroquine, including but not limited to, any of the following:

    • Systemic lupus
    • Rheumatoid arthritis
    • Porphyria cutanea tarda
    • Malaria treatment or prophylaxis
  • Evidence of other active malignancy, except:

    • Basal cell or squamous cell carcinoma of the skin
    • Treated carcinoma in situ
  • Uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Uncontrolled ongoing infection
    • HIV
    • Hepatitis B infection
    • Known G6PD deficiency
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Uncontrolled cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
    • Active GvHD
  • Inability to understand or unwillingness to sign the informed consent document
  • Concurrent anti-myeloma therapy within:

    • 7 days of prior corticosteroids
    • 14 days of prior antimyeloma agents, including thalidomide or lenalidomide
    • 28 days of a different investigational regimen
    • 14 days of any radiation
  • Women of child-bearing who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 30 days after the last dose of study drug.
  • Women who are pregnant or breastfeeding.
  • History of G6PD deficiency
  • HIV infection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01689987

Locations
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Amy Bedford       bedforda@ohsu.edu   
Principal Investigator: Emma Scott, M.D.         
Sponsors and Collaborators
OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01689987     History of Changes
Other Study ID Numbers: IRB00008296
Study First Received: September 17, 2012
Last Updated: August 5, 2013
Health Authority: United States: Food and Drug Administration

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
Cyclophosphamide
Sirolimus
Everolimus
Hydroxychloroquine
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on April 15, 2014