A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma

NCT01101594 | Terminated Phase 1

• 1 other identifier: IM-T-hLL1-DOX-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

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.

Conditions

Multiple Myeloma

Keywords

Treatment; Multiple Myeloma; Relapsed, refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• All patients administered any dose of study drug will be included in the evaluation of safety

  The frequency and severity of adverse events (AEs) will be tabulated by MedDRA Preferred Term and System Organ Class (SOC) for each dose group. AEs will be classified using the MedDRA version 8.0 with severity assessed by NCI CTC v3 toxicity grades

  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 (1)

• Determine the therapeutic efficacy of hLL1-DOX in this patient population

  During treatment and the changes at 4, 8 and 12 weeks after treatment and then every 3 months for up to 2 years

Study Arms (1)

hLL1-DOX

EXPERIMENTAL

4 Different dose levels of hLL1-DOX will be studied in groups of 3-6 patients. Once an optimal dose has been found, up to additional 30 patients will be studied at that dose level.

Drug: hLL1-DOX (the doxorubicin conjugate of milatuzumab)

Interventions

hLL1-DOX (the doxorubicin conjugate of milatuzumab) DRUG

hLL1-DOX will be administered intravenously (through a vein) on days 1, 4, 8 \& 11 every 21 days for up to 8 treatment cycles. 4 different dose levels of hLL1-DOX will be studied for safety and tolerability.

Also known as: hLL1-DOX, Milatuzumab-DOX, CD74-DOX

hLL1-DOX

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (5)

MD Anderson Orlando

Orlando, Florida, 32806, United States

Location

Georgia Cancer Specialists

Atlanta, Georgia, 30068, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University Hospital of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Center

Houston, Texas, 77030, United States

Location

Related Publications (8)

• 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.

  PMID: 14695162 BACKGROUND

• 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.

  PMID: 15475450 BACKGROUND

• 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.

  PMID: 2663143 BACKGROUND

• 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.

  PMID: 20101022 BACKGROUND

• 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.

  PMID: 16033844 BACKGROUND

• 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.

  PMID: 17875789 BACKGROUND

• 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.

  PMID: 19053886 BACKGROUND

• 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.

  PMID: 19351768 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: March 11, 2010
• First Posted: April 12, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: August 16, 2021

Record last verified: 2020-03

Locations

US (5)