Allogeneic Stem Cell Transplant for CLL

NCT01629511 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 2012-0249NCI-2018-01798P30CA016672
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose and side effects of gemcitabine and how well it works with clofarabine and busulfan and donor stem cell transplant in treating participants with chronic lymphocytic leukemia. Drugs used in chemotherapy, such as gemcitabine, clofarabine, and busulfan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. 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. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation Recipient; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Richter Syndrome

Outcome Measures

Primary Outcomes (2)

• 100 Day Treatment Related Mortality (TRM)

  Number of deaths related to treatment by day 100 post allogeneic transplant

  100 days post transplant

• Maximum Tolerated Dose (MTD)

  To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan \& Clofarabine

  Enrollment up to day 30 post transplant

Secondary Outcomes (1)

• Overall Survival

  Up to 1 year post transplant

Other Outcomes (3)

• Progression-free Survival (PFS)

  Up to 1 year post transplant

• Time-to-engraftment

  30 days post transplant

• Acute and Chronic Graft Verse Host Disease (GvHD)

  Up to 1 year post transplant

Study Arms (1)

Treatment (combination chemotherapy, stem cell transplant)

EXPERIMENTAL

Participants receive gemcitabine IV over 10-25 minutes on days -6 and -4, clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to -1. Starting day -2, participants receive tacrolimus PO daily for up to 6 months. Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim SC QD beginning 1 week after transplant until blood cell levels return to normal.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-Thymocyte Globulin; Drug: Busulfan; Drug: Clofarabine; Biological: Filgrastim; Drug: Gemcitabine; Drug: Methotrexate; Drug: Tacrolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo stem cell transplant

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

Treatment (combination chemotherapy, stem cell transplant)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

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

Treatment (combination chemotherapy, stem cell transplant)

Busulfan DRUG

Given IV

Also known as: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum, Busulfex, Busulphan, CB 2041, CB-2041, Glyzophrol, GT 41, GT-41, Joacamine, Methanesulfonic Acid Tetramethylene Ester, Methanesulfonic acid, tetramethylene ester, Mielucin, Misulban, Misulfan, Mitosan, Myeleukon, Myeloleukon, Myelosan, Mylecytan, Myleran, Sulfabutin, Tetramethylene Bis(methanesulfonate), Tetramethylene bis[methanesulfonate], WR-19508

Treatment (combination chemotherapy, stem cell transplant)

Clofarabine DRUG

Given IV

Also known as: Clofarex, Clolar

Treatment (combination chemotherapy, stem cell transplant)

Filgrastim BIOLOGICAL

Given SC

Also known as: FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Treatment (combination chemotherapy, stem cell transplant)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (combination chemotherapy, stem cell 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 (combination chemotherapy, stem cell transplant)

Tacrolimus DRUG

Given PO

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

Treatment (combination chemotherapy, stem cell transplant)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with chronic lymphocytic leukemia, prolymphocytic leukemia, or Richter's transformation who are eligible for allogeneic transplantation and are not eligible for protocols of higher priority
• A 10/10 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor
• Left ventricular ejection fraction (EF) \> 40%
• Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and corrected diffusion capacity of the lung for carbon monoxide (DLCO) \> 40%
• Serum creatinine \< 1.6 mg/dL
• Serum bilirubin \< 2 X upper limit of normal
• serum glutamate pyruvate transaminase (SGPT) \< 2X upper limit of normal
• Voluntary signed, written Institutional Review Board (IRB)-approved informed consent
• Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study

You may not qualify if:

• Patient with active central nervous system (CNS) disease
• Pregnant (positive 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
• Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV)-I, hepatitis B, or hepatitis C
• Active uncontrolled bacterial, viral or fungal infections
• Patient has received other investigational drugs within 1 week before enrollment

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

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic

Interventions

Antilymphocyte Serum; thymoglobulin; Busulfan; Clofarabine; Filgrastim; Granulocyte Colony-Stimulating Factor; Gemcitabine; Methotrexate; merphos; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines; Macrolides; Lactones

Limitations and Caveats

Early termination leading to small number of subjects analyzed. This study never moved to Phase II, therefore was not analyzed.

Results Point of Contact

• Title: Dr. Chitra Hosing
• Organization: UT MD Anderson Cancer Center

cmhosing@mdanderson.org

713-792-8750

Study Officials

• Chitra Hosing

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: June 27, 2012
• Study Start: November 21, 2012
• Primary Completion: April 25, 2018
• Study Completion: April 25, 2018
• Last Updated: February 24, 2020
• Results First Posted: February 10, 2020

Record last verified: 2020-02

Locations

US (1)