Clinical Trial: NCT01664910 - My Cancer Genome

NCT01664910

Description:

This phase I/II trial studies the side effects and the best dose of inotuzumab ozogamicin when given together with fludarabine phosphate, bendamustine hydrochloride, and rituximab before donor stem cell transplant in treating patients with lymphoid malignancies. Giving chemotherapy drugs, such as fludarabine phosphate and bendamustine hydrochloride, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cell and helps stop the patient's immune system from rejecting the donor's stem cells. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune system response against the body's normal cells. Giving fludarabine phosphate and bendamustine hydrochloride before the transplant together with anti-thymocyte globulin and tacrolimus may stop this from happening.

Related Conditions:

B-Cell Neoplasm

Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT01664910

Trial Eligibility

Document

Title

Brief Title: CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
Official Title: Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

Clinical Trial IDs

ORG STUDY ID: 2012-0265
SECONDARY ID: NCI-2012-02072
SECONDARY ID: 2012-0265
SECONDARY ID: P30CA016672
NCT ID: NCT01664910

Conditions

Hematopoietic and Lymphoid Cell Neoplasm

Interventions

Drug	Synonyms	Arms
Anti-Thymocyte Globulin	Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin	Treatment (transplant)
Bendamustine Hydrochloride	Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda	Treatment (transplant)
Fludarabine Phosphate	2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586	Treatment (transplant)
Inotuzumab Ozogamicin	Besponsa, CMC-544, Way 207294, WAY-207294	Treatment (transplant)
Methotrexate	Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039	Treatment (transplant)
Rituximab	ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83	Treatment (transplant)
Tacrolimus	FK 506, Fujimycin, Hecoria, Prograf, Protopic	Treatment (transplant)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To characterize the safety of anti-cluster of differentiation (CD) 22 immunoconjugate
      inotuzumab ozogamicin (CMC-544), when administered in conjunction with fludarabine
      (fludarabine phosphate), bendamustine (bendamustine hydrochloride), and rituximab as
      non-myeloablative preparative regimen for allogeneic stem cell transplantation for
      CD22-positive lymphoid malignancies.

      SECONDARY OBJECTIVES:

      I. To estimate tumor response. II. To determine overall and event-free survival rates by
      histology subtype.

      OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

      Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, and
      fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1
      hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6
      hours on days -6, 1, and 8 and patients with matched unrelated donors (MUD) receive
      anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive
      tacrolimus IV over 24 hours continuously or orally (PO) daily beginning on days -2 to 180
      followed by taper in the absence of graft-versus-host disease (GVHD) and methotrexate IV over
      30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo
      allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.

      After completion of study treatment, patients are followed up periodically.

Trial Arms

Name	Type	Description	Interventions
Treatment (transplant)	Experimental	Patients receive inotuzumab ozogamicin IV over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with MUD receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or PO daily beginning on days -2 to 180 followed by taper in the absence of GVHD and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic BM or PBSC transplant on day 0.	Anti-Thymocyte Globulin Bendamustine Hydrochloride Fludarabine Phosphate Inotuzumab Ozogamicin Methotrexate Rituximab Tacrolimus

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with B-cell hematological malignancies who are eligible for allogeneic
             transplantation

          -  Patients must have a fully-matched sibling donor or a matched unrelated donor
             identified

          -  Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology
             Group (ECOG)

          -  Left ventricular ejection fraction (EF) >= 45% with no uncontrolled arrhythmias or
             symptomatic heart disease

          -  Forced expiratory volume in one second (FEV1) >= 50%

          -  Forced vital capacity (FVC) >= 50%

          -  Corrected diffusion capacity of the lung for carbon monoxide (DLCO) >= 50%

          -  Serum creatinine < 1.6 mg/dL

          -  Serum bilirubin < 2 mg/dL upper limit of normal (unless due to Gilbert's disease;
             patient with this disease should have a right upper quadrant ultrasound evaluation
             before treatment)

          -  Serum glutamate pyruvate transaminase (SGPT) < 2 x upper limit of normal

          -  Men and women of reproductive potential must agree to follow accepted birth control
             methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with
             spermicide, condom with spermicide, or abstinence) for the duration of the study

          -  Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing
             potential (defined as not post-menopausal for 12 months or no previous surgical
             sterilization) or currently breast-feeding; pregnancy testing is not required for
             post-menopausal or surgically sterilized women

        Exclusion Criteria:

          -  Patient with active central nervous system (CNS) involvement

          -  Known infection with human immunodeficiency virus (HIV), human T-cell lymphotropic
             virus (HTLV)-I, hepatitis B, or hepatitis C

          -  Patients with other malignancies diagnosed within 2 years prior to study registration;
             skin squamous or basal cell carcinoma are exceptions

          -  Active bacterial, viral or fungal infections

          -  History of stroke within 6 months

          -  History of biliary colic attack

          -  A prior autologous transplant within 3 months of study entry or allogeneic stem cell
             transplant

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Patient has received other investigational drugs within 3 weeks before study
             registration

          -  Serious nonmalignant disease which, in the opinion of the investigator would
             compromise protocol objectives

          -  Prior exposure to CMC-544 within past 6 months

          -  Established refractoriness to CMC-544

Maximum Eligible Age:	70 Years
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Maximum-tolerated dose (MTD) of inotuzumab ozogamicin
Time Frame:	Up to 30 days
Safety Issue:
Description:	Defined as the highest dose for which the probability of toxicity is closest to 30%.

Secondary Outcome Measures

Measure:	Objective overall response (complete remission and partial remission)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Estimated with a 95% confidence interval in the dose that is declared the MTD. Logistic regression will be used to assess the association between response and disease and clinical characteristics of interest.

Measure:	Overall survival (OS)
Time Frame:	Up to 3 years
Safety Issue:
Description:	Kaplan-Meier survival curves will be used to estimate OS. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.

Measure:	Recurrence-free survival
Time Frame:	Up to 3 years
Safety Issue:
Description:	Kaplan-Meier survival curves will be used to estimate recurrence-free survival. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.

Measure:	Cumulative incidence of acute and chronic graft versus host disease (GVHD)
Time Frame:	Up to 3 years
Safety Issue:
Description:	The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.

Details

Phase:	Phase 1/Phase 2
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

February 27, 2020

Clinical Trials /

CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies