Clinical trial NCT01101594: A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma
Official title: A Phase I/II Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Treatment
Multiple Myeloma
Relapsed, refractory multiple myeloma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-04-12
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a Ph I trial to test the safety of the study drug, hLL1-DOX at different dose levels in patients with recurrent multiple myeloma. HLL1 is also known as milatuzumab and is attached to doxorubicin in this clinical trial.

Detailed description: In this clinical research trial, hLL1-DOX will be administered on days 1, 4, 8 and 11. This treatment cycle will be repeated every 3 weeks as long as patients continue to tolerate it, for a maximum of 8 treatment cycles (approximately 6 months).

Eligibility criteria: Inclusion Criteria:

* Able to provide signed, informed consent;
* Male or female, \>/= 18 years old;
* Multiple myeloma with one or more criteria for measurable disease (serum M protein \> 0.5 gm/dl, urinary M protein excretion \> 200 mg/24 hours, serum free light chain measurement \>20 mg/dl,);
* Refractory or relapsed to at least two prior standard systemic anti-myeloma treatment regimens one of which must include either thalidomide, lenalidomide or bortezomib;
* Adequate performance status (Karnofsky Scale \>/= 70%);
* Life expectancy at least 6 months;
* Adequate cardiac function: MUGA scan or 2D-ECHO with LVEF 55%, EKG with no medically relevant arrhythmia uncontrolled on medications;
* Adequate hematologic status within 2 weeks before study drug administration:
* Hemoglobin \>/=8.0 g/dL and platelets \>/=75,000/mm3 (both without transfusion or other hematologic support within 7 days of laboratory testing)
* White blood count (WBC) \>/= 2,000/mm3and absolute neutrophil count (ANC) \>/=1,500/mm3 (both without the use of colony stimulating factors within 7 days of laboratory testing);
* Adequate renal function: serum creatinine \</+ 2.5 mg/mL;
* Adequate hepatic function
* AST and ALT \</= 2.5 x the ULN
* Total bilirubin \</= 1.5 x the ULN

Exclusion Criteria:

* 1. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test Pregnancy testing is not required for post-menopausal or surgically sterilized women;
* Patients who are eligible for stem cell transplant.
* Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last hLL1-dox infusion;
* Prior local radiotherapy within 14 days; chemotherapy or kyphoplasty within 21 days, immunotherapy, plasmapheresis, or major surgery within 28 days; prior stem cell transplant within 12 weeks.
* Must have no persistent ≥ Grade 2 toxicity from prior treatments;
* Prior treatment with any other therapeutic agents for MM or investigational agents within 4 weeks, unless off study, and agreed by Sponsor;
* A history of allergic or adverse reactions to anthracycline/anthracenedione agents;
* Cumulative life-time anthracycline/anthracenedione exposure exceeding 300 mg/m2 (including daunorubicin, idarubicin, epirubicin or mitoxantrone);
* Known to be HIV positive, or any prior hepatitis B or C infection;
* Any history of clinically significant autoimmune disease (e.g., collagen vascular disorders, autoimmune hepatitis, Coombs positive anemia/thrombocytopenia, etc.)
* Prior history of mediastinal or pericardial external beam radiation therapy.
* Prior history of treatment with trastuzumab, unless discussed with and agreed to by Medical Monitor.
* Systemic infection or requiring anti-infectives within 7 days before first dose of study drug;
* Substance abuse or other concurrent medical conditions that, in the Investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study.

Primary outcomes:
measure: All patients administered any dose of study drug will be included in the evaluation of safety
timeFrame: Before infusion, 5 min after start, every 15 min until completion, then 30, 60, 90 and 120 min later of each dose of study drug
Secondary outcomes:
measure: Determine the therapeutic efficacy of hLL1-DOX in this patient population
timeFrame: During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years
Other outcomes:
Locations:
city: Orlando
country: United States
facility: MD Anderson Orlando
state: Florida
city: Atlanta
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Philadelphia
country: United States
facility: University Hospital of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Center
state: Texas
Study officials:
References:
citation: Griffiths GL, Mattes MJ, Stein R, Govindan SV, Horak ID, Hansen HJ, Goldenberg DM. Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res. 2003 Dec 15;9(17):6567-71.
citation: Burton JD, Ely S, Reddy PK, Stein R, Gold DV, Cardillo TM, Goldenberg DM. CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res. 2004 Oct 1;10(19):6606-11. doi: 10.1158/1078-0432.CCR-04-0182.
citation: Pawlak-Byczkowska EJ, Hansen HJ, Dion AS, Goldenberg DM. Two new monoclonal antibodies, EPB-1 and EPB-2, reactive with human lymphoma. Cancer Res. 1989 Aug 15;49(16):4568-77.
citation: Stein R, Gupta P, Chen X, Cardillo TM, Furman RR, Chen S, Chang CH, Goldenberg DM. Therapy of B-cell malignancies by anti-HLA-DR humanized monoclonal antibody, IMMU-114, is mediated through hyperactivation of ERK and JNK MAP kinase signaling pathways. Blood. 2010 Jun 24;115(25):5180-90. doi: 10.1182/blood-2009-06-228288. Epub 2010 Jan 25.
citation: Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, Hansen HJ, Horak ID, Griffiths GL, Goldenberg DM. Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res. 2005 Jul 15;11(14):5257-64. doi: 10.1158/1078-0432.CCR-05-0204.
citation: Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang CH, Burton J, Govindan S, Goldenberg DM. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5556s-5563s. doi: 10.1158/1078-0432.CCR-07-1167.
citation: Mark T, Martin P, Leonard JP, Niesvizky R. Milatuzumab: a promising new agent for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2009 Jan;18(1):99-104. doi: 10.1517/13543780802636162.
citation: Stein R, Smith MR, Chen S, Zalath M, Goldenberg DM. Combining milatuzumab with bortezomib, doxorubicin, or dexamethasone improves responses in multiple myeloma cell lines. Clin Cancer Res. 2009 Apr 15;15(8):2808-17. doi: 10.1158/1078-0432.CCR-08-1953. Epub 2009 Apr 7.