Post Transplant Donor Lymphocyte Infusion

NCT00167180 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2004LS006MT2003-150401M55207
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers.

Conditions

Leukemia, Myeloid, Chronic; Lymphomas; Multiple Myeloma; Myelodysplastic Syndrome; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; AML

Keywords

donor lymphocyte infusions; BMT; bone marrow transplant

Outcome Measures

Primary Outcomes (1)

• Number of Patients Alive

  The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.

  1 Year

Secondary Outcomes (4)

• Number of Patients Alive Without Disease

  1 Year

• Number of Participants With Complete Remission

  one year

• Number of Patients With Acute Graft-Versus-Host Disease

  Day 100

• Number of Patients With Bone Marrow Aplasia

  Day 100

Study Arms (2)

CML

ACTIVE COMPARATOR

Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion.

Procedure: Donor Lymphocyte Infusion

Non-CML or CML that Relapsed after Donor Lymphocyte Infusion

ACTIVE COMPARATOR

Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI.

Procedure: Donor Lymphocyte Infusion; Drug: Induction Chemotherapy

Interventions

Donor Lymphocyte Infusion PROCEDURE

donor cells infused over 2 hrs at cell dose of 0.5 dx 10\^8 CD3+T-cells/kg

Also known as: DLI

CML; Non-CML or CML that Relapsed after Donor Lymphocyte Infusion

Induction Chemotherapy DRUG

Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV

Also known as: Fludara, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Non-CML or CML that Relapsed after Donor Lymphocyte Infusion

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (age \> or = 1 years) with a diagnosis of relapse after related or unrelated allogeneic stem cell transplantation for a hematological malignancy.
• For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).
• For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix 3. Relapse can be determined morphologically with less than 5 percent blasts if definitive relapse can be determined. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.
• Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas) are NOT eligible for this protocol.
• For Chronic Phase CML patients only
• \- must have failed (no response in 3 months or incomplete response at 6 months) or refused treatment with Gleevec
• \- if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI with chemotherapy per this protocol will be offered
• Patients must be within one year of identification of relapse or if beyond that time period, must have at least 10% donor DNA by RFLP or cytogenetics.
• Same allogeneic donor (sibling or URD) used for transplantation is available for lymphocyte donation.
• No severe organ damage (by laboratory or clinical assessment) as measured by:
• \- blood creatinine ≤ 2.0 mg/dL
• \- liver function tests \< 5 x normal
• \- left ventricular ejection fraction \> 40% (testing required only if symptomatic or prior known impairment).
• \- pulmonary functions \> 50% (testing required only if symptomatic or prior known impairment). Oxygen saturation (\>92%) can be used in child where PFT's cannot be obtained.
• \- chest x-ray without evidence of active infection

You may not qualify if:

• Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing treatment at the time of relapse will be ineligible.
• Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other immunosuppressive medications are not eligible until these medications are discontinued for at least 2 weeks without a flare of GVHD.
• Active CNS leukemia
• Active fungal infection or pulmonary infiltrates (stable prior treated disease is allowable)
• HIV positive

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• Miller JS, Weisdorf DJ, Burns LJ, Slungaard A, Wagner JE, Verneris MR, Cooley S, Wangen R, Fautsch SK, Nicklow R, Defor T, Blazar BR. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood. 2007 Oct 1;110(7):2761-3. doi: 10.1182/blood-2007-05-090340. Epub 2007 Jun 19.

  PMID: 17579184 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma; Multiple Myeloma; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Induction Chemotherapy; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Jeffrey Miller
• Organization: Masonic Cancer Center, University of Minnesota

mille011@umn.edu

612-625-7409

Study Officials

• Jeffrey Miller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 14, 2005
• Study Start: January 1, 2004
• Primary Completion: November 21, 2017
• Study Completion: December 24, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 11, 2017

Record last verified: 2019-07

Locations

US (1)