Hydroxychloroquine and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT00568880 | Completed Phase 1 FDA Drug

• 1 other identifier: UPCC 01407
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  This is assessed using International Working Group criteria.

  Day 1 of each cycle (each cycle is 21 days)

Secondary Outcomes (2)

• Effects of regimen on the autophagy pathway

  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

  Day 1 and 8 of the first cycle and on Day 1 of each subsequent treatment cycle (each cycle is 21 days)

Study Arms (1)

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.

Drug: bortezomib; Drug: hydroxychloroquine

Interventions

bortezomib DRUG

bortezomib 1.0-1.3mg/m2 IV

Also known as: Velcade

Hydroxychloroquine Added to Bortezomib

hydroxychloroquine DRUG

hydroxychloroquine 200 mg pill

Also known as: Plaquenil

Hydroxychloroquine Added to Bortezomib

Eligibility Criteria

• Age: 18 Years - 120 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 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

You may not qualify if:

• 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)
• 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
• 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.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

Related Publications (1)

• 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.

  PMID: 24991834 RESULT

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Hydroxychloroquine

Condition Hierarchy (Ancestors)

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dan Vogl, MD

  Abramson Cancer Center at Penn Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2007
• First Posted: December 6, 2007
• Study Start: September 8, 2010
• Primary Completion: June 22, 2011
• Study Completion: June 22, 2011
• Last Updated: February 7, 2020

Record last verified: 2020-02

Locations

US (1)