CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL)

NCT01134575 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2009-0872NCI-2011-01699
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if CMC-544 given alone, and possibly given in combination with rituximab, can help to control the disease in patients with ALL. The safety of the study drug(s) will also be studied.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Relapsed; Refractory; Acute Lymphoblastic Leukemia; ALL; Burkitt's lymphoma; Lymphoblastic lymphoma; CMC-544; Inotuzumab Ozogamycin; Rituxan; Rituximab

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Response

  Primary endpoint for efficacy is response which is defined as: Complete Remission (CR), Complete Remission without recovery of counts (CRi) or Partial Remission (PR). Complete remission (CR): Disappearance of all clinical and/or radiologic evidence of disease. Neutrophil count \> 1.0 x109/L, platelet count \>100x109/L, and normal marrow differential (\< 5% blasts). 8.2 Complete remission without recovery of counts (CRi): Peripheral blood and marrow results as for CR, but with incomplete recover of counts (platelets \< 100 x 109/L; neutrophils \< 1 x 109/L). Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 25% abnormal cells in the marrow.

  After cycle 2, for up to 8 cycles

Study Arms (3)

Period 1: CMC-544 (Inotuzumab Ozogamycin) 1.3mg/m^2

EXPERIMENTAL

First patients \> 16 years and \< 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m\^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m\^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m\^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m\^2 IV (by vein) over 2-6 hours every 3-4 weeks.

Drug: CMC-544 (Inotuzumab Ozogamycin); Drug: Rituximab

Period 3: Weekly CMC-544 (Inotuzumab Ozogamycin)

EXPERIMENTAL

CMC-544 (Inotuzumab Ozogamycin) 0.8 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 1, 0.5 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 8, and 0.5 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 15. Weekly doses can be given at + 1 day. Course may be repeated every 3 weeks. Rituximab will be given on Day 1 and CMC-544 on Day 2 of the first dose; with subsequent weekly doses, both will be given weekly, rituximab preceding CMC-544. The weekly dose of rituximab will be 375 mg/m2.

Drug: CMC-544 (Inotuzumab Ozogamycin); Drug: Rituximab

Period 2: CMC-544 (Inotuzumab Ozogamycin) 1.8mg/m^2

EXPERIMENTAL

First patients \> 16 years and \< 16 years receive CMC-544 (Inotuzumab Ozogamycin) at a dose of 1.3 mg/m\^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m\^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m\^2 IV over 1 hour every 4 week cycle. With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m\^2 IV (by vein) over 2-6 hours every 3-4 weeks.

Drug: CMC-544 (Inotuzumab Ozogamycin); Drug: Rituximab

Interventions

CMC-544 (Inotuzumab Ozogamycin) DRUG

First patients \> 16 years and \< 16 years receive CMC-544 at a dose of 1.3 mg/m\^2 by vein (IV) over 1 hour during Course 1, and 1.8 mg/m\^2 IV over 1 hour during Course 2 and subsequently. In all other patients beginning dose of 1.8 mg/m\^2 IV over 1 hour every 4 week cycle. Part 2 CMC-544 (Inotuzumab Ozogamycin) 0.8 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 1, 0.5 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 8, and 0.5 mg/m\^2 IV over 1 hour (+ 15 minutes) on Day 15. Weekly doses can be given at + 1 day. Course may be repeated every 3 weeks. Rituximab will be given on Day 1 and CMC-544 on Day 2 of the first dose; with subsequent weekly doses, both will be given weekly, rituximab preceding CMC-544. The weekly dose of rituximab will be 375 mg/m2.

Period 1: CMC-544 (Inotuzumab Ozogamycin) 1.3mg/m^2; Period 2: CMC-544 (Inotuzumab Ozogamycin) 1.8mg/m^2; Period 3: Weekly CMC-544 (Inotuzumab Ozogamycin)

Rituximab DRUG

With no improvement after 2 courses of CMC-544, addition of Rituximab dose 375 mg/m\^2 IV (by vein) over 2-6 hours every 3-4 weeks.

Also known as: rituxan

Period 1: CMC-544 (Inotuzumab Ozogamycin) 1.3mg/m^2; Period 2: CMC-544 (Inotuzumab Ozogamycin) 1.8mg/m^2; Period 3: Weekly CMC-544 (Inotuzumab Ozogamycin)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously treated ALL (including Burkitt's lymphoma and lymphoblastic lymphoma) in relapse or primary refractory. Patients in first relapse will be eligible regardless of the first remission duration. At least 10 patients in Salvage 1-2 will be treated to assess anti-ALL response more precisely.
• Age 16 years or older. Pediatric patients (\<16 years old) will be allowed into the study after safety is established, that is at least 10 adult patients having received 1 or more cycles each.
• Zubrod performance status 0-3.
• Adequate liver function (bilirubin \</= 1.5 mg/dL and Alanine transaminase (SGPT) or Aspartate transaminase (SGOT) \</= 3 x upper limit of normal \[ULN\], unless considered due to tumor), and renal function (creatinine \</= 2 mg/dL). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is \</= 2.0 mg/dL and creatinine \</= 3 mg/dL.
• Male and female patients who are of childbearing potential agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 14 days of study start (applies only if patient is of childbearing potential. Non-childbearing is defined as \>/= 1 year postmenopausal or surgically sterilized).

You may not qualify if:

• Patient with active heart disease (NYHA class \>/= 3 as assessed by history and physical examination).
• Patients with a cardiac ejection fraction (as measured by either Radionuclide angiography (MUGA) or echocardiogram) \< 45% are excluded.
• Patients who receive other chemotherapy. Patients must have been off previous therapy for \>/= 2 weeks and must have recovered from acute toxicity (to grade 1 or less) of all previous therapy prior to enrollment (consent signing). (Concurrent therapy for central nervous system \[CNS\] prophylaxis or treatment for CNS relapse is permitted). Treatment may start earlier if necessitated by the patient's medical condition (e.g. rapidly progressive disease) following discussion with the Principal Investigator.
• Prior allogeneic stem cell transplant in previous 4 months.
• Peripheral lymphoblasts \> 50 x 10\^9/L.
• Pregnant and breast-feeding patients are excluded.
• Patients with known hepatitis B are excluded.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Zhao Y, Short NJ, Kantarjian HM, Chang TC, Ghate PS, Qu C, Macaron W, Jain N, Thakral B, Phillips AH, Khoury J, Garcia-Manero G, Zhang W, Fan Y, Yang H, Garris RS, Nasr LF, Kriwacki RW, Roberts KG, Konopleva M, Jabbour EJ, Mullighan CG. Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. Blood. 2024 Jul 4;144(1):61-73. doi: 10.1182/blood.2024023930.

  PMID: 38551807 DERIVED

• Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O'Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012 Apr;13(4):403-11. doi: 10.1016/S1470-2045(11)70386-2. Epub 2012 Feb 21.

  PMID: 22357140 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Burkitt Lymphoma

Interventions

Inotuzumab Ozogamicin; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Results Point of Contact

• Title: Hagop M. Kantarnian, MD/Chair
• Organization: The University of Texas MD Anderson Cancer Center

hkantarjian@mdanderson.org

713-792-7026

Study Officials

• Hagop Kantarjian, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study started as a single arm study of Inotuzumab Ozogamicin administered at two different dose levels. The protocol was later amended to modify to weekly Inotuxumab Ozogamicin administration.

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: June 2, 2010
• Study Start: June 4, 2010
• Primary Completion: April 18, 2018
• Study Completion: April 18, 2018
• Last Updated: July 16, 2024
• Results First Posted: May 22, 2019

Record last verified: 2024-07

Locations

US (1)