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

NCT01664910 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 2012-0265NCI-2012-02072
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated Dose (MTD) of Inotuzumab Without DLT

  Number of participants received inotuzumab in each cohort without DLT

  Up to 30 days

Secondary Outcomes (2)

• Overall Response

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

Study Arms (1)

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.

Procedure: Allogeneic Bone Marrow Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Bendamustine Hydrochloride; Drug: Fludarabine Phosphate; Biological: Inotuzumab Ozogamicin; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: Rituximab; Drug: Tacrolimus

Interventions

Allogeneic Bone Marrow Transplantation PROCEDURE

Undergo allogeneic BM transplant

Also known as: Allo BMT, Allogeneic BMT

Treatment (transplant)

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC or BM transplant

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (transplant)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Treatment (transplant)

Bendamustine Hydrochloride DRUG

Given IV

Also known as: Bendamustin Hydrochloride, Cytostasan Hydrochloride, Levact, Ribomustin, SyB L-0501, Treanda

Treatment (transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 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 BIOLOGICAL

Given IV

Also known as: Besponsa, CMC-544, Way 207294, WAY-207294

Treatment (transplant)

Methotrexate DRUG

Given IV

Also known as: 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)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (transplant)

Rituximab BIOLOGICAL

Given IV

Also known as: 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 DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (transplant)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Antilymphocyte Serum; thymoglobulin; Bendamustine Hydrochloride; fludarabine phosphate; Inotuzumab Ozogamicin; Methotrexate; merphos; Peripheral Blood Stem Cell Transplantation; Rituximab; CT-P10; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Aminopterin; Pterins; Pteridines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Antibodies, Monoclonal, Murine-Derived; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Issa Khouri, MD/Stem Cell Transplantation and Cellular Therapy Department
• Organization: The University of Texas MD Anderson Cancer Center

ikhouri@mdanderson.org

713-745-0049

Study Officials

• Issa Khouri

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: August 10, 2012
• First Posted: August 14, 2012
• Study Start: October 29, 2012
• Primary Completion: June 28, 2023
• Study Completion: June 28, 2023
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2024-06

Locations

US (1)