Clinical trial NCT00003163: Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma or Other B-cell Cancers
Official title: Myeloblative Therapy With Autologous Hematopoietic Stem Cell Transplantation in Patients With Multiple Myeloma and B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Keywords: refractory multiple myeloma
Waldenström macroglobulinemia
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
primary systemic amyloidosis
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-04-18
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation in treating patients who have multiple myeloma or other B-cell cancers.

Detailed description: OBJECTIVES:

* Determine the safety and efficacy of myeloablative therapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma and other B-cell malignancies.
* Determine the efficacy and pretransplantation prognostic factors associated with myeloablative therapy in these patients.
* Determine engraftment kinetics of granulocytes and platelets, as well as blood product transfusion requirements following hematopoietic stem cell transplantation.

OUTLINE: Patients must have hematopoietic stem cell procurement completed prior to myeloablative therapy. Patients receive high dose chemotherapy with autologous hematopoietic stem cell transplantation and supportive care. Melphalan is administered in one dose on day -1 at least 12 hours before stem cell infusion. Peripheral blood stem cells and/or bone marrow is reinfused on day 0. Filgrastim (G-CSF) or sargramostim (GM-CSF) is administered beginning on day 1 posttransplantation and continuing until blood counts recover.

Patients who are not candidates for tandem transplant may receive melphalan plus total body irradiation (TBI). Melphalan is administered IV on day -4. Total body irradiation is administered three times a day on days -3 and -2 and twice on day -1. At least 4 hours must elapse between each treatment. Hematopoietic stem cells are reinfused on day -1 upon completion of TBI or on day 0.

If patient is ineligible for melphalan plus TBI, the alternative single high dose regimen of melphalan plus cyclophosphamide is administered. Melphalan, for these patients, is given in two equal doses on day -4 followed by two consecutive days of cyclophosphamide on days -3 and -2. Hematopoietic stem cells are reinfused on day 0.

A second transplant may be considered, preferably between 3 and 6 months after the first transplant. The preferred regimen for the second transplant is melphalan alone or melphalan plus TBI as described above. The alternative regimens for the second dose therapy are melphalan alone or melphalan plus cyclophosphamide. For patients receiving melphalan alone, melphalan is administered in one dose on day -1 at least 12 hours before stem cell infusion. Hematopoietic stem cells are reinfused on day 0 for both alternative regimens.

Patients are followed for response from treatment for a minimum of 4 weeks and then periodically for survival.

PROJECTED ACCRUAL: A minimum of 10 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed multiple myeloma or other B-cell malignancy including non-Hodgkin's lymphoma, Waldenstrom's macroglobulinemia, or amyloidosis

  * Non-Hodgkin's lymphoma with T-cell immunophenotypes included

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 2,000/mm\^3 (unless due to disease)
* Platelet count at least 100,000/mm\^3 (unless due to disease)

Hepatic:

* Not specified

Renal:

* Not specified

Cardiovascular:

* LVEF at least 40%

Pulmonary:

* DLCO or FVC and FEV1 at least 50% of predicted unless due to restriction from volume loss secondary to disease

Other:

* HIV negative
* No overt infection or unexplained fever requiring broad spectrum antibiotics
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 2 weeks since prior biologic therapy

Chemotherapy:

* At least 2 weeks since other prior chemotherapy and recovered

Endocrine therapy:

* At least 2 weeks since prior endocrine therapy
* Concurrent steroids allowed

Radiotherapy:

* Not specified

Surgery:

* Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: David H. Vesole, MD, PhD
role: STUDY_CHAIR
References: