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Prolymphocytic LeukemiaPhase 1/2NCT00005803

Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation, Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation and Carmustine in people with Prolymphocytic Leukemia and Recurrent Adult Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation and Carmustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
5 sitesin 2 countries
Study dates
Sep 1999to Oct 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin's lymphoma) with primary refractory or relapsed disease after standard chemotherapy at high risk of relapse with conventional autografting; patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL
  • Must have an HLA genotypically or phenotypically identical related donor or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search
  • Cross-over to other tandem autologous-allogeneic research protocol (#2241) will be allowed if the patient loses the suitable HLA-matched related or unrelated donor but has an available HLA-haploidentical donor before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Cross-over from other tandem autologous-allogeneic research protocol (#2241) will be allowed if a suitable HLA-matched related or unrelated donor is identified before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study
  • Signed informed consent
  • Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization regimen
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  • Expected survival >= 3 months from study entry
  • DONOR: HLA genotypically or phenotypically identical related donor
  • DONOR: Must consent to granulocyte-colony stimulating factor (G-CSF) (filgrastim) administration and leukapheresis for both PBSC allograft and subsequent donor lymphocyte infusion (DLI)
  • DONOR: Must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)
  • DONOR: Age < 75 years (yrs), older donors may be considered after review at Patient Care Conference
  • DONOR: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be grades 1.0 to 2.1; unrelated donors who are prospectively: matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion
  • DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
  • DONOR: Only G-CSF mobilized peripheral blood mononuclear cells (PBMC) only will be permitted as a hematopoietic stem cell (HSC) source on this protocol

Who cannot join

  • Life expectancy severely limited by disease other than lymphoma
  • Prior autologous hematopoietic stem cell transplant
  • Patients at high risk of veno-occlusive disease of the liver (criteria not yet rigorously defined but includes bilirubin > 2.0 mg and serum glutamic oxaloacetic transaminase [SGOT] or serum glutamate pyruvate transaminase [SGPT] > 2 x normal); patients may be accepted outside of this range if cleared by gastrointestinal (GI) consult
  • Cardiac ejection fraction (EF) < 40% on multi-gated acquisition (MUGA) scan or cardiac echocardiogram (echo) (or if unable to obtain ejection fraction, shortening fraction of < 26%); patients with active or a history of cardiac disease should be evaluated with appropriate cardiac studies and/or consult; ejection fraction is required if age > 50 years or there is a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
  • Baseline serum-creatinine > 2.0 mg/dl and a calculated or measured creatinine clearance of < 50 ml/minute
  • Seropositive for the human immunodeficiency virus (HIV)
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  • Pulmonary dysfunction as measured by a corrected diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted total lung capacity (TLC) < 30%, forced expiratory volume in 1 second (FEV1) < 30% and/or receiving supplementary continuous oxygen; the FHCRC principal investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules
  • Pregnancy or breast-feeding
  • Patients with poorly controlled hypertension despite hypertensive medication
  • Karnofsky score less than 60; pediatric criteria: Lansky Play-Performance Score < 40
  • Patients with cluster of differentiation (CD)34 selected auto grafts
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Human immunodeficiency virus (HIV) seropositivity
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet FHCRC criteria for stem cell donation
  • DONOR: Donor (or centers) who will exclusively donate marrow

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • VA Puget Sound Health Care System

    Seattle, Washington, 98101

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

Germany1 site

  • Universitaet Leipzig

    Leipzig, D-04103

Other trials in Germany

About this study

Official title: A Phase I/II Study of Autologous Stem Cell Transplantation Followed by Nonmyeloablative Allogeneic Stem Cell Transplantation for Patients With Relapsed or Refractory Lymphoma - A Multi-center Trial

This phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy) +/- fludarabine (fludarabine phosphate), 90 mg/m^2 and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.

II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting.

SECONDARY OBJECTIVES:

  1. To determine the disease free survival and overall survival of non-myeloablative allografting following autologous PBSCT.

OUTLINE:

CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.

NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients with related donors) or 100 (patients with unrelated donors) followed by taper to day 180. Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day 96 (patients with unrelated donors).

Some patients may undergo donor lymphocyte infusion if there is evidence of disease progression and no evidence of graft-vs-host disease (GVHD).

After completion of study treatment, patients are followed up at day 180, 1 year, 1.5 years, 2 years, 3 years, and then annually thereafter.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation, Carmustine, Cyclophosphamide, Cyclosporine
Medical subject headings
Leukemia, Prolymphocytic, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Leukemia, Prolymphocytic, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Autologous Stem Cell Transplantation

    Undergo autologous transplantation

  • Autologous-Allogeneic Tandem Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called auto-allo HCT

    Undergo autologous-allogeneic tandem hematopoietic stem cell transplantation

  • CarmustineDrug

    Also called BCNU, Becenum, Becenun, BiCNU

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given PO

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

    Undergo allogeneic transplantation

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

    Undergo allogeneic transplantation

  • Therapeutic Autologous LymphocytesBiological

    Also called Autologous T-cells

    IV donor lymphocyte infusion

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo radiotherapy

Study groups in NCT00005803
Study groupRoleWhat they receive
Treatment (tandem transplantation)ExperimentalSee Detailed Description
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Procedure: Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Cytarabine; Drug: Etoposide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: Therapeutic Autologous Lymphocytes; Radiation: Total-Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Engraftment of HLA Identical PBSC Allografts

    Number of patients who engrafted by Day 56 post allogeneic transplant. Failure to engraft is defined as the absence of detectable donor cells in the marrow. The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).

    Measured: Day 56

  2. Non-Relapse Mortality

    The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease).

    Measured: Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting

Secondary outcomes (2)

  1. Overall Survival (OS)

    Number of patients surviving by interval. Chemosensitive and chemoresistant subjects will be analyzed separately.

    Measured: From the date of autologous transplant until the time of death, assessed up to 3 years

  2. Progression Free-survival (PFS)

    Number of patients surviving without disease by interval. Chemosensitive and chemoresistant subjects will be analyzed separately.

    Measured: From the date of autologous transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, assessed up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startSep 1999
  3. Primary completionJan 2016
  4. Study completionOct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005803
Sponsor's protocol ID
1409.00
Other IDs
NCI-2010-00130, 1409.00, P30CA015704
Status last verified
Dec 2019
First submitted
2 Jun 2000
Last updated
29 Jan 2020
Data monitoring committee
Yes

Publications

  • Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

    PubMed 32499241

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous Hematopoietic Stem Cell Transplantation, Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation and Carmustine in people with Prolymphocytic Leukemia and Recurrent Adult Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Engraftment of HLA Identical PBSC Allografts (time frame: Day 56). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00005803, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2020.

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