Hydroxychloroquine, Cyclophosphamide, Dexamethasone, and Sirolimus in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT01689987 | Completed Phase 1 DMC

• 5 other identifiers: IRB00008296NCI-2012-01754CR00022154MR00041096P30CA069533
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of hydroxychloroquine when given together with cyclophosphamide, dexamethasone, and sirolimus in treating patients with multiple myeloma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as hydroxychloroquine, may stimulate the immune system in different ways and stop cancer cells from growing. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping them from spreading. Giving hydroxychloroquine together with sirolimus, cyclophosphamide, and dexamethasone may be a better treatment for multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• MTD of hydroxychloroquine defined as the highest dose at which 0/6 or 1/6 subjects experience a dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0

  Incidence of DLTs will be tabulated for each dose level. Summarized using descriptive statistics or frequency distributions, as appropriate.

  56 days

Secondary Outcomes (4)

• Duration of overall response

  Time that measurement criteria are met for response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 months

• Myeloma response (stringent complete response, complete response, very good partial response, partial response, stable disease, and progressive disease), as assessed by the International Myeloma Working Group

  Up to 12 months

• Progression-free survival

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 12 months

• Time to response

  Time from the first day of therapy until the time that measurement criteria are met for response, assessed up to 12 months

Other Outcomes (2)

• Mean percentage of p70S6 myeloma cells

  Up to day 5 of course 2

• Number of autophagic vesicles per bone marrow plasma cells

  Up to day 5 of course 2

Study Arms (1)

Treatment (HCQ, sirolimus, cy/dex)

EXPERIMENTAL

Patients receive hydroxychloroquine PO daily on days 1-28 (days 5-28 of course 1), sirolimus PO on days -2 to 4, and cyclophosphamide IV continuously and dexamethasone PO on days 1-4. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Hydroxychloroquine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (HCQ, sirolimus, cy/dex)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (HCQ, sirolimus, cy/dex)

Hydroxychloroquine DRUG

Given PO

Treatment (HCQ, sirolimus, cy/dex)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (HCQ, sirolimus, cy/dex)

Pharmacological Study OTHER

Correlative studies

Treatment (HCQ, sirolimus, cy/dex)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, RAPAMYCIN, SILA 9268A, WY-090217

Treatment (HCQ, sirolimus, cy/dex)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed multiple myeloma
• Documented relapse or persistent disease after at least 1 prior therapy containing both bortezomib and lenalidomide; or at least 2 prior therapies containing bortezomib in one and lenalidomide in the other, or if intolerant of bortezomib and/or lenalidomide; prior autologous and allogeneic bone marrow transplantation are allowed
• Need for further treatment for myeloma, as determined by the patient's treating physician; 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)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• 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)

You may not qualify if:

• 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 hours (hrs) prior to first dose of Rapamycin:
• Carbamazepine
• Rifabutin
• Rifampin
• Rifapentine
• St. John's wort
• Clarithromycin
• Cyclosporine
• Diltiazem
• Erythromycin
• Itraconazole
• Fluconazole
• Ketoconazole
• Telithromycin

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Hydroxychloroquine; Sirolimus

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Study Officials

• Emma Scott

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 17, 2012
• First Posted: September 21, 2012
• Study Start: September 1, 2012
• Primary Completion: April 1, 2016
• Last Updated: September 7, 2017

Record last verified: 2017-08

Locations

US (1)