Multiple Myeloma and Plasma Cell NeoplasmPhase 1NCT00568880
Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing bortezomib and hydroxychloroquine in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- bortezomib and hydroxychloroquine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2010to 22 Jun 2011
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed multiple myeloma
- Documented relapse or continued disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)
- Need for further therapy for myeloma, as determined by the patient's treating physician
- Age greater than 18 years
Who cannot join
- Baseline peripheral neuropathy of grade 2 or higher
- History of allergic reactions to compounds of similar chemical or biologic composition to bortezomib or hydroxychloroquine
- Prior dose-limiting toxicity with bortezomib
- Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis. Patients with well-controlled psoriasis may participate in the study provided that they are under the care of a specialist in this condition who agrees to monitor the patient for exacerbations.
- Other conditions that would require therapy with hydroxychloroquine, including but not limited to systemic lupus, rheumatoid arthritis, porphyria cutanea tarda, and malaria treatment or prophylaxis
- ECOG performance status >2 (for definition, see section 0)
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- Life expectancy of less than 3 months
- Lack of adequate organ or bone marrow function based on lab values drawn ≤ 14 days before beginning treatment.
- Concurrent treatment with a different investigational regimen. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
- Treatment with other anti-myeloma agents, including thalidomide or lenalidomide, within the 14 days prior to initiating hydroxychloroquine. Treatment with corticosteroids will be permitted up to 7 days prior to initiating hydroxychloroquine. Corticosteroids that are being used for other diseases are permitted if the dose is less than the equivalent of 20 mg of prednisone daily. Concurrent therapy with bisphosphonates through the study period is permitted at the discretion of the treating physician. Concurrent hematopoietic growth factors are also permitted, including filgrastim or pegfilgrastim, epoetin alpha, and darbepoetin alpha
- Known central nervous system involvement. The poor prognosis and progressive neurological dysfunction associated with central nervous system involvement would confound the evaluation of neurological and other adverse events. The presence of calvarial lytic lesions or plasmacytomas is not an exclusion criterion if there is no central nervous system involvement.
- Concurrent malignancy other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, any carcinoma in situ, or localized prostate adenocarcinoma (stage T1a or T1b) with a stable PSA for a period of at least 4 months. Patients with a prior malignancy treated with chemotherapy, biologic agents, and/or radiation are eligible for this study if they have completed therapy ≥4 years previously with no evidence of recurrent disease. Patients with a prior malignancy treated with surgery alone are eligible for this study if they have completed therapy ≥2 years previously with no evidence of recurrent disease.
- Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Inability to understand the informed consent document or unwillingness to consent. Written informed consent must be obtained from all patients before study entry.
- Pregnancy or breastfeeding.
- Unwillingness to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation for men and women of child-bearing potential.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104-4283
About this study
Official title: A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with bortezomib and to see how well it works in treating patients with relapsed or refractory multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- To establish the dose-limiting toxicities and maximum tolerated dose of hydroxychloroquine when added to a standard-dose regimen of bortezomib for treatment of patients with relapsed or refractory multiple myeloma.
Secondary
- To obtain a preliminary estimate of the toxicity rate and response rate of this combination at the maximum tolerated dose.
- To confirm preclinical evidence showing synergistic effects of hydroxychloroquine and bortezomib by correlating response rate with blood levels of hydroxychloroquine and degree of autophagy inhibition in repeated bone marrow samples.
OUTLINE: This is a phase I dose-escalation study of hydroxychloroquine followed by a phase II study.
- Phase I: Patients receive oral hydroxychloroquine every other day for 2 weeks. Patients then receive oral hydroxychloroquine 1-3 times daily or every other day and bortezomib IV twice a week for 2 weeks. Treatment with hydroxychloroquine and bortezomib repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) for hydroxychloroquine is determined, additional patients are accrued to the phase II portion of the study.
- Phase II: Patients receive hydroxychloroquine (at the MTD determined in phase I) and bortezomib as in phase I.
Blood and bone marrow samples are collected periodically during the study for correlative studies by mass spectrometry, proteasome inhibition assays, pharmacokinetic analysis and assessment of aggresome formation, autophagy inhibition, and apoptosis by protein electrophoresis and serum free light-chain analysis.
After completion of study treatment, patients are followed periodically.
- Being tested
- bortezomib, hydroxychloroquine
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called Velcade
bortezomib 1.0-1.3mg/m2 IV
Also called Plaquenil
hydroxychloroquine 200 mg pill
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine Added to Bortezomib | Experimental | Dose escalated by cohorts Hydroxychloroquine 200-600 mg pill every other day. Bortezomib 1.0-1.3mg/m2 IV, days 1, 4, 8, and 11 of each 21 day cycle. Receives: Drug: bortezomib; Drug: hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
This is assessed using International Working Group criteria.
Measured: Day 1 of each cycle (each cycle is 21 days)
Secondary outcomes (2)
Effects of regimen on the autophagy pathway
Measure peripheral blood mononuclear cells
Measured: at baseline, prior to bortezomib on Day1 and 8 of cycle 1, prior to bortezomib on Day 1 of cycle 2 (each cycle is 21 days)
AV accumulation during therapy
mean AVs / Bone Marrow plasma cell
Measured: Day 1 and 8 of the first cycle and on Day 1 of each subsequent treatment cycle (each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2007 (estimated)
- Study start8 Sep 2010
- Primary completion22 Jun 2011
- Study completion22 Jun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dan Vogl, MD, Study chair, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00568880
- Sponsor's protocol ID
- UPCC 01407
- Status last verified
- Feb 2020
- First submitted
- 5 Dec 2007
- Last updated
- 7 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, Paul TM, Nichols CW, Porter DL, Kaplan J, Mallon G, Bradner JE, Amaravadi RK. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy. 2014 Aug;10(8):1380-90. doi: 10.4161/auto.29264. Epub 2014 May 20.
PubMed 24991834
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Hydroxychloroquine Added to Bortezomib for Relapsed/Refractory Myeloma
- ClinicalTrials.gov ID
- NCT00568880
- Acronym / sponsor ID
- UPCC 01407
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 8 Sep 2010 (actual)
- Primary completion
- 22 Jun 2011 (actual)
- Study completion
- 22 Jun 2011 (actual)
- First posted
- 6 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with bortezomib and to see how well it works in treating patients with relapsed or refractory multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- To establish the dose-limiting toxicities and maximum tolerated dose of hydroxychloroquine when added to a standard-dose regimen of bortezomib for treatment of patients with relapsed or refractory multiple myeloma.
Secondary
- To obtain a preliminary estimate of the toxicity rate and response rate of this combination at the maximum tolerated dose.
- To confirm preclinical evidence showing synergistic effects of hydroxychloroquine and bortezomib by correlating response rate with blood levels of hydroxychloroquine and degree of autophagy inhibition in repeated bone marrow samples.
OUTLINE: This is a phase I dose-escalation study of hydroxychloroquine followed by a phase II study.
- Phase I: Patients receive oral hydroxychloroquine every other day for 2 weeks. Patients then receive oral hydroxychloroquine 1-3 times daily or every other day and bortezomib IV twice a week for 2 weeks. Treatment with hydroxychloroquine and bortezomib repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) for hydroxychloroquine is determined, additional patients are accrued to the phase II portion of the study.
- Phase II: Patients receive hydroxychloroquine (at the MTD determined in phase I) and bortezomib as in phase I.
Blood and bone marrow samples are collected periodically during the study for correlative studies by mass spectrometry, proteasome inhibition assays, pharmacokinetic analysis and assessment of aggresome formation, autophagy inhibition, and apoptosis by protein electrophoresis and serum free light-chain analysis.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine Added to Bortezomib | Experimental | Drug: bortezomib, Drug: hydroxychloroquineDose escalated by cohorts Hydroxychloroquine 200-600 mg pill every other day. Bortezomib 1.0-1.3mg/m2 IV, days 1, 4, 8, and 11 of each 21 day cycle. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically confirmed multiple myeloma
- Documented relapse or continued disease after at least one prior therapy (which may include autologous and allogeneic bone marrow transplantation)
- Need for further therapy for myeloma, as determined by the patient's treating physician
- Age greater than 18 years
Key exclusion criteria (16 listed)
- Baseline peripheral neuropathy of grade 2 or higher
- History of allergic reactions to compounds of similar chemical or biologic composition to bortezomib or hydroxychloroquine
- Prior dose-limiting toxicity with bortezomib
- Known macular degeneration or retinopathy (diabetic or otherwise), porphyria, or psoriasis. Patients with well-controlled psoriasis may participate in the study provided that they are under the care of a specialist in this condition who agrees to monitor the patient for exacerbations.
- Other conditions that would require therapy with hydroxychloroquine, including but not limited to systemic lupus, rheumatoid arthritis, porphyria cutanea tarda, and malaria treatment or prophylaxis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomibAlso: Velcadebortezomib 1.0-1.3mg/m2 IV | Drug | Hydroxychloroquine Added to Bortezomib |
| hydroxychloroquineAlso: Plaquenilhydroxychloroquine 200 mg pill | Drug | Hydroxychloroquine Added to Bortezomib |
Primary outcome
Overall response rate
Time frame: Day 1 of each cycle (each cycle is 21 days)
This is assessed using International Working Group criteria.
2 secondary outcomes
Effects of regimen on the autophagy pathway
Time frame: at baseline, prior to bortezomib on Day1 and 8 of cycle 1, prior to bortezomib on Day 1 of cycle 2 (each cycle is 21 days)
AV accumulation during therapy
Time frame: Day 1 and 8 of the first cycle and on Day 1 of each subsequent treatment cycle (each cycle is 21 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2020.
- Results publication: PubMed 24991834Vogl DT, Stadtmauer EA, Tan KS, Heitjan DF, Davis LE, Pontiggia L, Rangwala R, Piao S, Chang YC, Scott EC, Paul TM, Nichols CW, Porter DL, Kaplan J, Mallon G, Bradner JE, Amaravadi RK. Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma. Autophagy. 2014 Aug;10(8):1380-90. doi: 10.4161/auto.29264. Epub 2014 May 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dan Vogl, MD study chair
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib and hydroxychloroquine in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Abramson Cancer Center at Penn Medicine 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 4 inclusion and 16 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 Feb 2020. 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?
Overall response rate (time frame: Day 1 of each cycle (each cycle is 21 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 NCT00568880, which also lists 1 linked publication.
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 Feb 2020.