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Recurrent Plasma Cell MyelomaPhase 1NCT01689987

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

A Phase 1 study testing Cyclophosphamide, Dexamethasone and Hydroxychloroquine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by OHSU Knight Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Dexamethasone and Hydroxychloroquine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
Sep 2012to Apr 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 55Show fewer
  • St. John's wort
  • Clarithromycin
  • Cyclosporine
  • Diltiazem
  • Erythromycin
  • Itraconazole
  • Fluconazole
  • Ketoconazole
  • Telithromycin
  • Verapamil
  • Voriconazole
  • Posaconazole
  • 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)
  • Absolute neutrophil count (ANC) =< 1.0 x 10^9/L
  • Platelets =< 50 x 10^9/L for any reason
  • Serum creatinine >= 2.5 mg/dL
  • Total or direct bilirubin >= 2.0 mg/dL
  • Transaminases 2 x the upper limit of normal
  • Fasting glucose >= 200 mg/dL
  • Serum potassium < 3.4 mmol/l
  • Serum phosphorus < 2.4 mg/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
  • Human immunodeficiency virus (HIV)
  • Hepatitis B infection
  • Known glucose-6-phosphate dehydrogenase (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 graft-versus-host disease (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
  • Known history of HIV infection

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase I Dose Escalation Study of Hydroxychloroquine With Infusional Cyclophosphamide, Pulse Dexamethasone and Rapamycin in Patients With Relapsed or Refractory Multiple Myeloma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of hydroxychloroquine (HCQ) in combination with rapamycin (sirolimus) and infusional cyclophosphamide and pulse dexamethasone (cy/dex) for patients with relapsed/ refractory multiple myeloma.

SECONDARY OBJECTIVES:

  1. To evaluate biological activity and efficacy of the combination of cyclophosphamide, dexamethasone, rapamycin and hydroxychloroquine in patients with relapsed/refractory multiple myeloma.

II. To determine whether this treatment regimen results in mammalian target of rapamycin (mTOR) and autophagy inhibition in primary myeloma cells during therapy and if this corresponds with treatment responses.

OUTLINE: This is a dose-escalation study of hydroxychloroquine.

Patients receive hydroxychloroquine orally (PO) daily on days 1-28 (days 5-28 of course 1), sirolimus PO on days -2 to 4, and cyclophosphamide intravenously (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.

After completion of study treatment, patients are followed up for 12 months.

Being tested
Cyclophosphamide, Dexamethasone, Hydroxychloroquine, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • HydroxychloroquineDrug

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, RAPAMYCIN

    Given PO

Study groups in NCT01689987
Study groupRoleWhat they receive
Treatment (HCQ, sirolimus, cy/dex)ExperimentalPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Hydroxychloroquine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 56 days

Secondary outcomes (4)

  1. Duration of overall response

    Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.

    Measured: 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

  2. 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

    Presented with two-sided 95% exact binomial confidence interval.

    Measured: Up to 12 months

  3. Progression-free survival

    Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.

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

  4. Time to response

    Will be summarized by 25th, 50th (median), and 75th percentile along with 95% confidence intervals using Kaplan-Meier method.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionApr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01689987
Sponsor's protocol ID
IRB00008296
Other IDs
NCI-2012-01754, CR00022154, MR00041096, IRB00008296, P30CA069533
Status last verified
Aug 2017
First submitted
17 Sep 2012
Last updated
7 Sep 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Dexamethasone and Hydroxychloroquine in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 56 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01689987.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2017.

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