Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

NCT00571662 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 0389-00-FB
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT).

Conditions

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Non-Hodgkins Lymphoma; Hodgkins Disease; Peripheral T-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Percent of Participants With Chimerism: Full Donor Chimerism Defined as >95% Donor CD3+ Cell in Blood as Assessed by DNA Fingerprinting

  the efficacy of the regimen as determined by engraftment rate and establishment of donor hematopoietic chimerism at day +28 and day +70.

  days +28 and +70

• Toxicity for the Combination of Pentostatin and Low Dose Total Body Irradiation (TBI)

  Conditioning regimen to count recovery (D + 28 post transplant)

Secondary Outcomes (3)

• Incidence of Acute and Chronic Graft-versus-host Disease

  twice weekly until day 100 up to 1 year post transplant

• Responses to Therapy

  every 6 mo. up to 2 years

• Kinetics of Immunologic Reconstitution

  at day 100 post transplantation

Study Arms (1)

Cohort I

EXPERIMENTAL

Pentostatin to be administered intravenously on days - 10, -9, and -8 at a dose of 4mg/m2/day

Drug: Pentostatin; Radiation: Total-body irradiation (TBI); Drug: Cyclosporine A (CsA); Drug: Mycophenolate Mofetil (MMF); Drug: G-CSF

Interventions

Pentostatin DRUG

4 mg/m\^2 intravenous(IV)once a day(QD)x3days (days -10, -9, -8)

Also known as: Nipent

Cohort I

Total-body irradiation (TBI) RADIATION

TBI will consist of 2.0 GY at 8-12cGy/min via 6MV photons delivered AP/PA fields, without lung blocks or via lateral fields with lucite compensator along the head and neck region. TLD (thermal luminescent dosimetry) will be used to verify dose uniformity. TBI will be given on day -1.

Cohort I

Cyclosporine A (CsA) DRUG

CsA will be given at 2.0 mg/kg intravenous (IV) Q 12hrs on days -1,0,and+1 (total 6 doses) then converted to oral at 2 mg/kg by mouth (PO) twice a day (BID) until day+80, then tapered 10% per week over approximately 3 months if no GVHD for related donor transplants. For unrelated CsA will be given at same dose and schedule until day+100 then tapered by 10% per week if no GVHD

Also known as: Neoral

Cohort I

Mycophenolate Mofetil (MMF) DRUG

MMF 15 mg/kg by mouth twice a day (PO BID) will be given from day 0-27 then stopped without tapering for related donor transplants. For unrelated donor transplants MMF will be given at same dose until day+40 then tapered over 2months. in absence of GVHD. Doses will be rounded to nearest 250 mg.

Cohort I

G-CSF DRUG

10 mcg/kg/day subcutaneously for at least 4 consecutive days.

Also known as: Leukine

Cohort I

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19-75 years
• Patients who relapse after autologous stem cell transplantation.
• Patients who are candidates for an autologous or conventional allogeneic stem cell transplantation from a disease standpoint but who do not qualify functionally (from the point of view of organ function, or performance status) for a myeloablative protocol.
• Any patient, where in the opinion of the primary treating oncologist, nonmyleoablative therapy would be the treatment option in the best patients interest providing the patient fits all other eligibility criteria for this protocol.
• Identification of a matched related or unrelated stem cell donor
• Diseases:
• Acute myelogenous leukemia first complete remission with high-risk cytogenetics\>second complete remission minimal residual disease (\<10% blasts\*). Acute lymphocytic leukemia first complete remission with high-risk cytogenetics \>second complete remission minimal residual disease (\<10% blasts\*). Chronic myelogenous leukemia first chronic phase, accelerated phase (\<10% blasts\*)blast phase with minimal residual disease (\<10% blasts\*)second chronic phase. Chronic lymphocytic leukemia recurrence after the front line regimen (related donor transplant), chemorefractory disease (unrelated donor transplant),T-CLL in partial remission or any minimal residual disease. Myelodysplastic syndromes refractory anemia with or without ringed sideroblasts,RAEB, RAEB-T, and CMML (\< than 10% blasts\*). \*both in peripheral blood and bone marrow
• Multiple myeloma - after receiving at least one regimen of prior chemotherapy
• Non-Hodgkin's Lymphomas:
• Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen (related donor transplant), or chemorefractory disease (related or unrelated donor transplant). Follicular Low-Grade Lymphoma, Marginal Zone Lymphomas (splenic, nodal, or extranodal/MALT type): chemorefractory disease or \> 2 prior regimens. Mantle Cell Lymphoma: first complete or partial remission, refractory disease, or failed prior ASCT. Diffuse Large B-cell Lymphoma, Follicular Large cell Lymphoma, Peripheral T-cell Lymphoma, Anaplastic Large Cell Lymphoma: refractory disease, or failed prior ASCT. Burkitt or Acute Lymphoblastic Lymphomas: high-risk disease in remission, chemosensitive persistent or recurrent disease. Cutaneous T-cell Lymphomas: (Mycosis Fungoides, Sezary Syndrome): chemorefractory disease of \> 2 prior regimens
• Hodgkins Disease: refractory or persistent disease and not candidate for ASCT, or failed prior ASCT.
• Peripheral T-cell Lymphoma

You may not qualify if:

• Age \> 75 years and \< 19 years
• progressive disease within 8 weeks of prior therapy or within 12 weeks after prior autologous stem cell transplantation
• Active CNS malignancy (patients with known positive CSF cytology or parenchymal lesions visible by CT or MRI)
• Fertile men or women unwilling to use appropriate contraceptive techniques during and for 12 months following treatment
• Females who are pregnant
• Patients who are HIV seropositive
• Active uncontrolled infection or immediate life-threatening condition at the time of enrollment
• Significant Organ dysfunction:
• Calculated Creatinine Clearance \<55ml/min
• cardiac ejection fraction \<40%, NYHA class II or greater cardiac disease.
• DLCO \< 40% , FEV1/FVC ratio \<50% predicted, or receiving supplementary continuous oxygen
• total bilirubin \> 2x upper limit of normal (unless due to Gilberts disease or malignancy), ALT and AST 4x the upper limit of normal
• Karnofsky score \<60%
• Patients with uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension, diabetes)
• HLA genotypically matched relative

Sponsors & Collaborators

• University of Nebraska: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Nebraska Medical Center, Section of Oncology/Hematology

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, T-Cell, Peripheral

Interventions

Pentostatin; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; Granulocyte Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma; Lymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: R Gregory Bociek
• Organization: University of Nebraska Medical Center

rgbociek@unmc.edu

402-559-5388

Study Officials

• Gregory Bociek, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: December 8, 2000
• Primary Completion: December 30, 2008
• Study Completion: December 30, 2008
• Last Updated: October 24, 2023
• Results First Posted: November 17, 2010

Record last verified: 2023-10

Locations

US (1)